Direct and Indirect Effects of Blue Light Exposure on Skin: A Review of Published Literature

Blue light is defined as light within the wavelength range of 400 nm (violet) to 500 nm (cyan) (Fig. 1) [1]. Blue light has lower energy than ultraviolet (UV) radiation (280–400 nm) and can reach further into the dermis, up to the depth of 1 mm [1, 2]. However, while the effects of UV radiation on skin have been widely studied, less is understood regarding the effects of blue light [3].

The sun is the main source of blue light, which is also emitted by electronic devices, such as computer monitors, flat-screen televisions, smartphones, tablets, and fluorescent light bulbs (Table 1). Changing lifestyles, with less time spent outdoors and increased use of light-emitting diode (LED) and fluorescent lighting and electronic screens via smartphones, televisions, computer monitors, and laptops, have changed the pattern of blue light exposure in humans [3].

Although the full range and exact nature of the biological effects of blue light are unknown, both beneficial and detrimental effects have been described [5]. In controlled clinical settings, blue light can be used to treat conditions such as psoriasis, atopic dermatitis, and acne [5]. However, the field of blue light therapy is still developing, and its discussion is beyond the scope of this article. While most of the research to date has focused on the effects of blue light on the eyes, less is known about its impact on the skin, where similar photoreceptors are found. Finally, the consequences of increased blue light exposure during night-time hours and disruptions to circadian rhythms are not well understood.

The objectives of this review were to describe the evidence on the impact of blue light on the skin, understand the quality of evidence provided by existing medical research, and consider options for how the skin might be protected from the detrimental effects of blue light.

The PubMed and ProQuest databases were searched in January 2022. Searches were restricted to clinical trials, systematic reviews, meta-analyses, and in vitro and in vivo studies reporting results in humans or non-clinical specimens. PubMed was searched using the term string ([“blue light” OR “blue-light” OR “violet-blue light” OR “high-energy visible light”] AND [skin OR dermatology OR dermatologic OR cutis OR cutaneous OR epidermis OR dermis]), producing 1,106 results. ProQuest was searched using the term string ([“blue light” OR “blue-light” OR “violet-blue light” OR “high-energy visible light”] AND [skin or derma* OR cutis or cutaneous or epiderm* or dermis]) and (la.exact[“English”]), producing 3,426 results. Titles and abstracts of identified articles were reviewed for inclusion. Search results were supplemented by articles considered relevant by the authors.

Blue light exerts its direct effects on the skin by interacting with chromophores, in which it triggers a change from a ground state to an activated state [5]. Chromophores responsible for the direct effects of blue light include flavins, porphyrins, nitrosated proteins, and opsins (Fig. 2; Table 2) [5]. Activation of these molecules results in overproduction of reactive oxygen species (ROS) and release of reactive nitrogen species, i.e., nitrogen monoxide (NO), and hyperpigmentation [5].

Multiple studies have shown that blue light exposure causes excessive ROS generation in cultured human keratinocytes and dermal fibroblasts, in medaka fish embryos, and in the skin of hairless mice and healthy human volunteers [6, 7, 9, 11-14, 16, 18-20]. The main chromophores responsible for blue light-induced ROS overproduction are believed to be flavins, such as flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), and porphyrins such as heme [5]. Mitochondria are one of the main intracellular locations of flavins [5]. Several studies have found that blue light-induced ROS generation was mostly restricted to the mitochondria, damaging mitochondrial DNA and disrupting respiration [9, 14, 20]. Furthermore, blue light has been shown to decrease the expression of genes regulating mitochondrial function, such as early growth response protein 1 (EGR1) and forkhead box protein O1 (FOXO1), in primary human keratinocytes and melanocytes [23]. However, other studies have shown that ROS produced as a result of blue light exposure can also damage nuclear DNA [16, 20]. Importantly, Chamayou-Robert et al. [21] have shown that blue light has clastogenic and aneugenic effects in human keratinocytes, resulting in stable and heritable aberrations. Blue light exposure has been shown to reduce flavin autofluorescence in the skin of human volunteers [14].

In addition to flavins and porphyrins, Mizutani et al. [13] have shown that both UV and blue light induce ROS generation from carbonylated proteins located in the stratum corneum. They found that ROS generation was induced by radiation in the range between 360 and 470 nm, suggesting that blue light has a greater contribution to ROS generation from carbonylated proteins located in the stratum corneum than UV [13]. Furthermore, Morvan et al. [10] have shown that blue light induces protein carbonylation in human skin explants. In experiments on hairless mice, blue light delayed permeability barrier recovery and reduced the thickness of the lipid layer located between the stratum corneum and stratum granulosum [27].

Blue light-induced ROS overproduction is associated with decreased cell viability and/or cell proliferation, increased proinflammatory signaling, and disrupted collagen metabolism [7, 10, 12, 16, 17, 20]. Dermal fibroblasts exposed to blue light exhibited general metabolic inhibition, reduced adenosine triphosphate (ATP) synthesis, impaired transforming growth factor-β (TGF-β) signaling, reduced procollagen I synthesis, and reduced collagen lattice contractility [9, 10]. Yoo et al. [17] showed that blue light suppressed proliferation in human keratinocytes by increasing the expression of the transient receptor potential vanilloid 1 (TRPV1) and downregulating the epidermal growth factor receptor (EGFR)/phosphoinositide 3-kinase (PI3K)/AKT/forkhead box O3a (FOXO3a) pathway. They have also shown that blue light causes an increase in ROS and tumor necrosis factor-α (TNF-α). Blue light also suppressed the expression of TP73, a gene involved in proliferation, in primary human keratinocytes and melanocytes [23]. Dong et al. [16] reported that, in addition to ROS overproduction, blue light irradiation increased the levels of proinflammatory cytokines interleukin (IL)-1α, IL-6, IL-8, and TNF-α in cultured human keratinocytes. The study by Liebel et al. [12] demonstrated that visible light irradiation of reconstituted human epidermis resulted in increased IL-1α and matrix metalloproteinase-1 (MMP-1) release. Morvan et al. [10] reported that blue light exposure increased cyclo-oxygenase-2 (COX-2) expression in human explants.

Blue light can cause photolysis of nitrosated proteins, but only in the presence of cupric ions (Cu²⁺), as blue light alone does not have the energy needed to break the covalent bond in N–O [31]. As a result of this reaction, NO is released, which induces differentiation in skin cells [24, 26, 30]. Liebmann et al. [24] have demonstrated that at wavelengths of 412–426 nm and high fluences, blue light is cytotoxic to human keratinocytes and skin-derived endothelial cells [26]. However, at 453 nm and at fluences of up to 500 J/cm², blue light inhibits proliferation by inducing differentiation, as shown by increased levels of involucrin and keratin-1 messenger RNA (mRNA) [26]. In a study conducted by Kim et al., blue light inhibited innate immune responses in human keratinocytes by inducing the S-nitrosylation of various proteins, including TIR-domain-containing adapter-inducing interferon-β (TRIF), Myd88, and nuclear factor-κ light chain enhancer of activated B cells (NF-κB) [30]. Blue light irradiation also blocked Toll-like receptor (TLR) 3- and TLR5-induced NF-κB phosphorylation, resulting in reduced levels of TLR-induced proinflammatory cytokines [30]. In humans, photolytic release of NO from nitrosated proteins is believed to be sufficient to cause significant local vasodilation and possibly even to reduce systemic blood flow [31].

Blue light is capable of causing pigmentation and hyperpigmentation of the skin, the latter of which can lead to mottled hyperpigmentation or age spots [19, 29]. A study conducted on 20 volunteers with skin types IV–VI found that, compared with UV, blue light produced darker hyperpigmentation that lasted longer [32]. While both UV and blue light cause hyperpigmentation via ROS generation, only blue light causes hyperpigmentation via opsin stimulation [10]. In skin biopsies from healthy volunteers, blue light irradiation over 5 consecutive days resulted in increased perinuclear vacuolization in keratinocytes and an increased number of melan-A-positive cells [10, 33]. Blue light irradiation increased melanin production, oxygen saturation, and hemoglobin content in female volunteers [29]. Skin darkening and erythema have also been observed after exposure to blue light [29, 34].

Opsins are a class of photosensitive G protein-coupled receptors, which regulate various signaling cascades [5]. In addition to the retina, opsins are expressed in the skin (Table 3) [5].

For example, Kim et al. [39] reported that rhodopsin is found in the plasma membrane of cultured human keratinocytes. The authors also showed that blue light irradiation increases rhodopsin expression, which, in turn, decreases the expression of keratinocyte differentiation markers keratin-1 and keratin-10 via the Gα_i pathway [39]. On the other hand, Gondran et al. [40] reported that blue light exposure reduced the levels of opsin (OPN) 1 short wave (OPN1 SW), OPN2, and OPN3 in cultured human keratinocytes.

Regazzetti et al. [28] identified OPN3 as the only opsin that was expressed at a significant level in human melanocytes. When exposed to blue light, OPN3 initiated a signaling cascade that included calcium-dependent activation of calcium/calmodulin-dependent protein kinase II (CAMKII), followed by activation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), extracellular signal-regulated kinase (ERK) and p38, leading to phosphorylation of microphthalmia-associated transcription factor (MITF) and, finally, increases in the enzymes tyrosinase and dopachrome tautomerase (DCT) that are responsible for melanogenesis [28]. Blue light-induced hyperpigmentation is more pronounced and persistent in people with darker skin (Fitzpatrick types III–VI), likely because they have higher levels of tyrosinase–DCT complexes than people with lighter skin (Fitzpatrick types I and II) [1].

In addition to directly affecting the skin, blue light can exert indirect effects on the body by disrupting the normal circadian rhythm. This occurs via both the central mechanism, which involves stimulation of light-sensing receptors located in the retina, and via the peripheral mechanism, which involves direct interaction with skin cells [5]. By disrupting the normal circadian rhythm, blue light can negatively affect the skin repair processes that take place during the night (Table 3) [41].

Melanopsin is a member of the opsin family found in the intrinsically photosensitive ganglion cells (ipRGCs) of the retina, which are responsible for adjusting the circadian rhythm of the body to the light/dark cycle [5]. Photostimulation of ipRGCs resets the circadian clock, reduces plasma melatonin levels, and suppresses melatonin synthesis [35-37]. The fact that melatonin receptors have been identified in multiple sites in the brain, as well as in other organs and tissues, including the heart, kidneys, pancreatic islets, adrenal glands, stomach, and gonads, suggests that melatonin has a wide range of physiological effects [36].

Multiple studies have shown that melanopsin is most efficiently stimulated by blue light (459–484 nm) [35], prompting concerns that blue light from artificial sources, including electronic devices, can disrupt the natural circadian rhythm [5]. Studies in humans suggest the potential for clinical effects, although data are limited. In a study conducted in 116 volunteers, exposure to room light (<200 lux, wavelengths were not specified) for 8 h before bedtime delayed the onset of the night-time melatonin increase and reduced its duration compared with exposure to dim light (<3 lux) [36]. Exposure to room light during the usual hours of sleep suppressed melatonin by more than 50% [36]. A subsequent study assessed the effects of prolonged (40 h) exposure to dim light (<8 lux), white light (250 lux, 2800 K), and blue-enriched white light (250 lux, 9000 K) in younger and older healthy volunteers [37]. White light and blue-enriched white light significantly reduced subjective sleepiness and delayed melatonin increase onset compared with dim light in both younger and older participants. Blue-enriched white light significantly reduced melatonin exposure only in younger participants, and significantly increased cortisol levels in older participants only [37].

In addition to melatonin, a number of peripheral mechanisms are involved in circadian rhythm regulation, including clock genes, such as bmal1 and per1, which are known to be expressed in skin cells [41, 42]. For example, blue light reduced the transcription level of per1 in human keratinocytes [16]. In addition, blue light altered the activation pattern of the external nicotinamide adenine dinucleotide phosphate oxidase (ECTO-NOX) in mice [38]. ECTO-NOX proteins appear to play a central role in the entrainment of the biological clock both by light and by melatonin, and are present in both plants and animals, including humans [38].

The circadian rhythm has been shown to affect multiple cellular and physiological processes occurring in the skin [41]. For example, the rate of blood flow, permeability to both hydrophilic and lipophilic compounds, and transepidermal water loss are all higher in the evening and at night than during the day [41]. On the other hand, sebaceous gland activity is highest during the day and decreases in the evening and at night [41]. Therefore, moisturizers and topical medications, such as corticosteroids, are more effective when used later in the day. Normal keratinocyte proliferation peaks at night, and this periodicity is lost in cancerous skin cells [41]. Interfollicular epidermal keratinocytes and hair follicle keratinocytes obtained from women with circadian rhythm dysregulation due to shift work have been shown to have reduced clonogenic potential [43]. Repair of sunlight-induced DNA damage also mostly occurs at night. One exception is the enzyme 8-oxoguanine DNA glycosylase (OGG1), which is involved in the base excision repair pathway and is most active in the morning. OGG1 levels are decreased in shift workers, suggesting that healthy sleep is required for its optimal functioning [41]. Therefore, the circadian rhythm influences multiple processes occurring in the skin, with most of the repair and regeneration taking place at night [41, 42].

Carotenoids are one of the main classes of antioxidants that protect the skin from ROS damage. Most of the carotenoids found in the skin absorb radiation in the blue section of the spectrum. The highest concentration of carotenoids in the skin is found in the lipid lamellae located in the stratum corneum, the outermost skin layer that serves as a permeability barrier, preventing transepidermal water loss [13, 44]. Several studies have shown that blue light irradiation causes degradation of carotenoids [11, 18, 19].

Most currently available sunscreens are designed to protect against UV radiation, and organic sunscreen agents predominantly absorb UVB radiation [34]. Tinted sunscreens that contain inorganic compounds such as iron oxides, titanium dioxide, and zinc oxide are able to provide protection against blue light radiation [34, 45].

When considering cosmetic interventions for protecting against blue light, a strategy of daytime protection and night-time repair may be optimal. An ideal regimen of daytime protection would include reduced exposure to blue light and prevention or minimization of free radical formation (Table 4) [22, 34, 46-51]. An ideal regimen of night-time repair would include greater protection of the opsin photoreceptors against activation, collagen against degradation, mitochondria against damage, and DNA against oxidation, as well as other methods (Table 4) [11, 29, 51-61].

The scientific understanding of the effects of blue light on the skin has improved in recent decades. However, several factors continue to limit the progress in this field, including variations in the definition of blue light itself. Methodological constraints include the use of different light sources, which often produce radiation outside blue light wavelengths, precluding the establishment of firm cause–effect connections and complicating comparisons between studies. Another limitation is the lack of understanding of the biological significance of the differences in the intensity of blue light radiation between natural and artificial sources. Furthermore, some authors contend that the magnitude and duration of exposure to blue light produced by the sun, indoor lighting sources, and various electronic devices in the course of normal day-to-day activities are insufficient to produce meaningful biological effects or to worsen lesions in melasma patients [4, 62]. While the intensity of blue light exposure from the sun is significantly higher than that generated by the screens of electronic devices, some chromophores, such as melanopsin, are particularly sensitive to blue light, and even low levels of irradiation may be able to induce significant effects [5]. Lastly, there is a lack of a widely adopted indicator of the ability of sunscreens to protect against blue light radiation. The sun protection factor (SPF), a common marker of sunscreen effectiveness, primarily reflects the UVB protection level [34]. The SPF shows how much energy is required to produce sunburn on sunscreen-protected skin compared with unprotected skin. Moseley et al. [47] developed a modified SPF, which they termed photosensitivity protection factor (PPF), which reflects the effects of visible-spectrum radiation on the skin of patients with photosensitivity to such radiation. However, a blue light-specific metric is still lacking.

Blue light is capable of producing various effects on the skin, including deleterious direct effects, such as hyperpigmentation and photoaging, and complex indirect effects, such as circadian rhythm modulation. The precise nature of how blue light affects the circadian rhythm is not fully understood. However, increased exposure to blue light due to the widespread use of electronic devices warrants further research attention, particularly because long-term exposure to artificial sources of blue light has the potential to produce clinical effects by altering melatonin signaling. Progress in this field is hampered by a lack of standardized methods, including the use of different sources of blue light and measures of its biological effects. Several strategies designed to protect against the negative effects of blue light are being explored, of which the most promising include daytime protection and night-time repair components.

The authors thank Dianne Vanessa Alejo, Anna Maria Vida Garcia, Allan Rey Martin Ignacio, Janina Felicity Jabonete, and Hubert Alex Untal (FMD K&L-Philippines) for support with the literature search, and Melissa Tang, Siti Shahera Anwar, Bo Yan, and Cecilia Li (Johnson & Johnson) for their help in the literature search and for reviewing the manuscript. Georgii Filatov of AMICULUM provided editorial and medical writing support for the development of this publication.

Orawan Suitthimeathegorn is an employee of Johnson & Johnson Pte. Ltd. Yanyun Ma, Cheng Yang, and Wei Liu have no conflicts of interest to disclose.

The costs of performing the literature review and developing this publication were funded by Johnson & Johnson Pte. Ltd. (2 Science Park Drive, #07-13, Ascent, Singapore Science Park 1, Singapore 118222).

Orawan Suitthimeathegorn performed the literature review, constructed the outline, and wrote the manuscript. Cheng Yang, Yanyun Ma, and Wei Liu shaped the outline and reviewed the manuscript. All the authors edited and approved the final revision of this paper for submission.

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.