Light therapies for regeneration, rejuvenation, and healing

Highlights:

• Light therapy aims to facilitate regeneration and recovery of tissues via exposing a patient to a particular kind of light
• Types of light therapy use light with different wavelengths, including bright white, ultraviolet, blue, yellow, green, red, near infra-red, and far infrared light
• Main areas of application include treatment of dermatological conditions, wound healing, precancerous and cancerous lesions, and skin rejuvenation
• Photodynamic therapy attracts much attention due to its regenerative potential and possible stimulation of brain function

Introduction

Our mood, sleep quality, and general mental condition are strongly influenced by the light levels in the environment. Tissues and cells in our bodies tend to respond in different ways to different wavelength depending on the depth of penetration. These observations led to the development of multiple techniques united under the term "light therapy" that employ light as an intervention. Nowadays light therapy is a method widely implemented in clinical practice across hospitals and health centers, and in multiple commercial wellness procedures.

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Types of light therapy

The modern physiotherapeutic application of light was introduced in the 1850s by Florence Nightingale (1). The method rose to popularity in 1903 after Niels Finsen developed the treatments for tuberculosis scarring with ultraviolet (UV) light and smallpox scarring with red light, for which he later received the Nobel Prize. Since the 1950s, light treatment has been widely applied by physiotherapists for dermatological conditions. Since the 1990s, the applications of light therapy have broadened, including supportive cancer care, depression treatment, surgery complications, and neurological diseases. 

Light therapy approaches can be classified according to the light wavelength and depth of skin penetration. The main types are listed in the table below, assuming that light-emitting diodes (LEDs) are used to produce light (2):

Different types of light therapy can be combined to reach a desirable effect. Laser treatment is frequently not included within the light therapy and is considered a separate intervention. This classification is mainly technical due to the different light characteristics depending on the source. Lasers frequently operate on higher power and produce monochromatic light, while LED light is produced within some bandwidths (~20 nm) and has lower power. Nevertheless, many biological effects have similar underlying mechanisms both for laser and light therapies.

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Bright white light 

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One of the most popular applications of bright white light therapy is connected with seasonal affective disorder (SAD) - a condition in which people cyclically suffer from depression symptoms at the same time of the year, most frequently in winter. Due to the lack of natural sunlight, the circadian clock may become dysregulated, leading to symptoms like excessive fatigue, oversleeping, and overeating. It is known that bright light can help suppress melatonin production in the pineal gland and, thereby, can attenuate many of the symptoms associated with SAD (3). Usage of artificial light that imitates naturally occurring daytime sunlight helps reset the circadian clock, thus alleviating the SAD symptoms. Clinical guidelines endorse using light therapy for SAD due to its safety and ease of application (4). Nussbaumer-Streit et al., in their extensive Cochrane review (5), assessed a range of papers with randomized clinical trials addressing the use of bright white light, infrared light, and no light treatment. The analyzed studies showed that white light and infrared light therapy reduced the incidence of SAD compared with no light therapy. However, the difference was statistically insignificant in many cases, the studies were methodology flawed, and the sample sizes were small. These drawbacks led the authors to conclude that light therapy against SAD has limited evidence.

Limited evidence also exists for the treatment of non-seasonal depression and other disorders. The meta-analysis by Penders et al. (6) included studies that reported RCTs (randomized clinical trials) comparing antidepressant pharmacotherapy with bright light therapy for ≥ 30 minutes to antidepressant pharmacotherapy without bright light therapy. Only studies with the treatment of non-seasonal depression were included. Studies of seasonal depression were excluded. Ten studies involving 458 patients showed improvement using bright light therapy augmentation versus antidepressant pharmacotherapy alone. In another meta-analysis, the authors analyzed papers addressing the light treatment of bipolar depression. The overall analysis showed a significant positive effect. However, the data were highly heterogeneous, and the number of RCTs was small (7). 

Bright light therapy has been also associated with improved cognitive function and mood both in healthy subjects, and in patients suffering from neurodegenerative disorders (8).

Ultraviolet 

UV light can be divided into several subranges recommended by ISO standard (9), the most well-known and most widely used being UVA (315-400 nm) and UVB (280-315 nm) ranges. The biological effects of UV depend on the range applied. UVB light reaches the epidermis and the upper epidermis and is mainly responsible for vitamin D synthesis. It induces local immunosuppressive effect  and is connected to induced cell arrest in skin cells (10), which allows its use for multiple dermatological conditions. Exposure to UVA light has a delayed effect compared to UVB and acts through modulation of various cytokines and enzymes, such as heme oxygenase-1 (HO-1) that mediates anti-inflammatory and anti-proliferative effects (11).

Since Finsen's discovery, UVB light has been an important treatment for multiple skin diseases, including psoriasis, neonatal jaundice, and atopic dermatitis (12). It mainly targets inflammatory skin processes by altering cytokine production and inducing apoptosis of infiltrating T-cells (13,14). UV radiation can protect the skin by inducing thickening of the stratum corneum (the outermost layer of the epidermis). Moreover, the antibacterial effect of UV light prevents or reduces skin colonization by harmful microorganisms, such as Staphylococcus aureus or Pityrosporum orbiculare. 

Multiple studies also reported a mood-enhancing effect of UV light (15,16). A primary mood-modulating effect of UVB range via the skin is through the vitamin D pathway. It is known that the major source of vitamin D for humans is the exposure of the skin to sunlight (UVB 280-315 nm), resulting in the conversion of 7-dehydrocholesterol to pre-vitamin D3. Furthermore, vitamin D receptors in the human brain (17) indicate that mood and depressive disorders might be directly influenced by vitamin D deficiency. In a meta-analysis by Veleva et al. (18), out of the seven included studies, six showed a positive effect of UV light on mood, depressive scores, or SAD. However, as in the case with the bright light therapy, the number of studies was small, as well as the number of participants in each study. Combined with the high heterogeneity of the results, these biases make it difficult to draw general conclusions about the effect of UV light on mood and depressive disorders, and the topic requires additional investigation.

UVA light is used more rarely, however, it is widely applied within the framework of the PUVA (psoralen and UVA) therapy. PUVA combines the use of the photosensitive compound psoralen with UV irradiation and is used to treat various skin diseases, including eczema, psoriasis, cutaneous T-cell lymphoma, and vitiligo (19).

Despite multiple applications of UV light, there are even more concerns connected to its long-term usage, including vision damage, skin aging, and its carcinogenic influence. All bands of UV light after the long exposure have harmful effects on the eyes, damage collagen fibers, destroy vitamin A, and accelerate skin aging. UVB was connected to the direct DNA damage (20) and increased risks of skin cancers. UVA has also been linked to the oncogenic risks through the indirect DNA damage caused by the reactive oxygen species (ROS).

Blue light

Blue light presents the safer alternative to UV light with similar effects. The effect of blue light is dependent on different chromophores (21) – molecules able to absorb light, such as endogenous nucleic acids, aromatic amino acids, cytochromes, melanin, etc. Through cytochrome c oxidase (a protein found in the membrane of mitochondria), blue light may affect mitochondrial function (22). Dungel et al. demonstrated that inhibited by NO (nitric oxide) mitochondrial function is reactivated after exposure to blue light (23).

Due to its anti-inflammatory properties, blue light is clinically used to treat acne, psoriasis, atopic dermatitis, and eczema, but the number of comprehensive studies is limited (24). The meta-analysis of existing studies shows, however, that blue light can be used as a safe and effective treatment with results compared to placebo control in acne and wound healing (25).

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Red light

Among the visible wavelengths, red light has the deepest tissue penetration and has been used to treat wounds, photodamage, precancers, and prevent oral mucositis in cancer patients (26). It is rarely used as a standalone frequent and mostly is combined with photosensitizing molecules such as aminolevulinic acid (ALA) and its derivatives. In a double-blind RCT by Sanclemente et al., red light therapy combined with ALA derivative demonstrated superior efficacy in the treatment of photodamage compared to placebo and light therapy alone (27). 

Red light combined with ALA derivatives seems to be a promising treatment option for premalignant and malignant lesions. Studies in patients with nonmelanoma skin cancer and basal cell carcinoma (28,29) showed a statistically significant improvement of lesions after the course of treatment.

Red light therapy was shown to regulate circadian rhytms and normalize sleeping patterns in patients, including patients with mild cognitive impairment and Alzheimer’s. Meta-studies show significant mild to moderate effects across multiple trials (30).

Infra-red

Monotherapeutic use of IR light is limited, however, there is a limited body of research (31) in patients with diabetes wounds, antibiotic-resistant Staphylococcus aureus, and pressure wounds. The IR light treatment in each case led to a decrease in pain, inflammation, and an increase in wound contraction. Beneficial effects of IR treatment combined with visible light were observed in some dermatological conditions, but more data are needed to estimate the prospects of such approaches (32).

Photobiomodulation

The light therapy method that has recently attracted much attention is photobiomodulation (PBM). PBM involves the use of red or near-infrared light at low power to stimulate cells or tissues. PBM is used to reduce pain and inflammation and to regenerate damaged tissue. PBM has gained recognition in various medical fields, including ophthalmology (33) and neurology (34).

Brain PBM therapy was shown to enhance the metabolic capacity of neurons and stimulate anti-inflammatory, anti-apoptotic, and antioxidant responses (35). Its therapeutic role in disorders such as dementia and Parkinson's disease, as well as to treat stroke, brain trauma, and depression, has gained increasing interest. PBM can be safely applied in elderly patients and has shown improvement in conditions such as dementia (36). Studies in humans have shown that PBM can improve electrophysiological activity and cognitive functions such as attention, learning, memory, and mood in older people (37). Altogether, this points to the perspective of PBM application as a multipurpose anti-aging treatment.

Similar to blue light, the main site of light absorption in PBM (38) is at the mitochondria and, specifically, cytochrome c oxidase. Near-infrared light is absorbed more and, consequently, the effect is more pronounced. Another putative mechanism involves the activation of light or heat-gated ion channels (membrane proteins that regulate ion transport). PBM is thought to enhance mitochondrial ATP production, cell signaling, and growth factor synthesis and regulate oxidative stress.

The review of existing literature by Glass (39) shows that a reasonable body of evidence supports PBM efficacy in skin rejuvenation, acne, wound healing, and alopecia. Nevertheless, due to small cohorts and methodological flaws, the quality of evidence should be further improved by additional research.

PBM is also widely used for cosmetical purposes. In a controlled trial study Wunsch et al. (40) demonstrated that after 30 sessions of PBM treatment subjects experienced intradermal collagen density increase. This effect was combined with improved skin complexion, reduction of fine wrinkles, and skin roughness.

Safety

Except for long-term UV light exposure, light therapy methods are considered mostly safe. Long-term UV light exposure, as considered above, can significantly increase the risk of skin cancer in any form (including the use of tan beds). Another concern is ocular discomfort and vision problems, which are reported in about 0% to 45% of participants in studies involving light therapy (41). However, no evidence was found for ocular damage due to light therapy, except for one case report of a person treated with the photosensitizing antidepressant clomipramine.

Recommendations

If you would like to recommend your client light therapy, there are several simple options that can be used both at home or at a clinic:

• Light box can be used for bright light therapy in home settings;
• Near-infrared, red, or blue light portable lamp;
• Infrared sauna (there are smaller options for homes).

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Conclusions

Light therapies present a range of safe and non-invasive methods that show their clinical potential against many conditions. The rising body of evidence, especially for photodynamic therapy, shows their positive impact on regeneration, healing, and cognitive function. This data suggest that light therapy may be adopted as a method for anti-aging and rejuvenation. However, for further development and adaptation, more research is needed. 

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DISCLAIMER: This article is based on incomplete scientific research. The presented methods lack robust evidence.
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