Prof. Dr. Vijai K.S. Shukla and Vaijnath Lad, International Cosmetics Science Centre A/S (ICSC) Denmark03.21.23
Social perceptions and value judgments are often based on appearance. Dull, tired skin is indicative of aging. Wrinkles, under-eye puffiness, uneven skin tone and volume loss around eyes, mid face and lips add years to one’s appearance. Aging is a complex phenomenon involving both intrinsic and extrinsic processes that contribute to a loss of structural integrity and physiological function of the skin. Factors contributing to aging can be divided into four main categories: biological, environmental, mechanical and lifestyle. We present here lifestyle and atmospheric factors which affect skin and overall health.
Trans fats found in processed foods like margarine and fast food can clog arteries, which takes away elasticity from the skin. High glycemic index foods such as bread, chips, popcorn and cake are rapidly digested and absorbed which causes rapid spikes in blood sugar levels. These spikes affect biochemical functions like the insulin pathway and may affect blood vessels and accelerate the aging process. High blood sugar levels can affect collagen tissues and make skin vulnerable to lines and wrinkles.
Artificial colors enhance the visual appeal of food and non-food products. Some synthetic colors, like tartrazine, have adverse effects on human health and especially young children. Tartrazine is an artificial lemon-yellow azo dye, recognized as E102 or C.I. 19140 or FD&C Yellow 5 and used for the coloring of food. Tartrazine may be found in nonfood products like soaps, cosmetics, shampoos and other hair products, crayons and stamp dyes. A diversity of immunologic reactions has been recognized in tartrazine consumption, comprising general fatigue, nervousness, migraines, clinical depression, purple skin spots and sleep disruption. Either consumption or cutaneous contact with a material containing tartrazine can produce symptoms of sensitivity.2
Pharmaceuticals are the major part of treatment of various disorders. Drugs can induce or enhance skin diseases such as phototoxicity, skin pigmentation, acne, itching and psoriasis. Drugs can cause hair disorders like alopecia. Penicillin, sulfa, phenyl-butazone and tetracycline are the most common drug inducing various skin disorders.3
Studies have clearly shown varying associations exist between tobacco or alcohol use, and skin photoaging and facial aging. Smoking generates free radicals which, in turn, damage skin repair mechanisms and reduce collagen and elastin synthesis, which leads to premature skin aging. In our studies, we saw a major decline in glutathione peroxidase clearly associated with smoking and alcohol. Smoking can also cause cutaneous micro vascular contraction that increases in relation to the duration and amount of exposure. Research shows alcohol dramatically affects appearance and skin features. Drinking alcohol causes dehydration, depleting skin blood’s capillaries flow. Chronic alcohol consumption has detrimental impacts on skin health, impairing the skin’s antioxidant defense system by decreasing dermal carotenoid concentrations. Alcohol also causes peripheral vasodilation, which can lead to dilated facial capillaries.4
Clinical observations have suggested that there is an intrinsic connection between psychological state and skin diseases. Chronic psychological stress stimulates the autonomic nervous system, renin-angiotensin system and the hypothalamic-pituitary-adrenal axis. Prolonged activation can result in chronic immune dysfunction, increased reactive oxygen species (ROS) production and DNA damage, which are known contributors to skin aging. Sleep deprivation affects features relating to the eyes, mouth, and skin. The investigators reported drooping eyelids; red, swollen eyes; dark circles under the eyes; pale skin, wrinkles/fine lines, and drooping corners of the mouth.
An analytic cross-section study was conducted on 400 subjects—200 patients with primary psychiatric disorders and 200 age- and sex-matched individuals free from primary psychiatric disorders. Researchers found that infectious skin diseases are the most common skin disease categories in psychiatric patients. Although psychogenic skin disorders occur exclusively in primary psychiatric disorder patients, it is much less frequent than the infectious skin diseases overall.6
An Australian Longitudinal Study, conducted on 6,630 women, highlights that the relationship between skin disease and psychological morbidity in young women. It confirms that psychological morbidity (depression, anxiety and stress) is a factor in the causation of skin disease.7
Chronic diseases are major killers in modern era. Physical inactivity is a primary cause of most chronic diseases. Conversely, physical activity prevents and delays chronic diseases, implying such diseases need not be the outcome of life.
Most commonly, pollutants are generated through the burning of fossil fuels by vehicles and industries giving rise to components such as particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs). Additional pollutants are derived from a variety of unrelated sources, such as cigarette smoke, ultraviolet (UV) light, volatile organic compounds (VOCs), and tropospheric (ground level) ozone. Particulate pollutants with a diameter of 2.5mm or less (PM2.5) and 10mm or less (PM10) and nano particles are the main constituents of PM. PAHs and VOCs are mainly generated by power plants, industries, vehicles and domestic agricultural sources.8
Epidemiological evidence that exposure to traffic-related air pollution including PM, NOx and ground level ozone is associated with pigment spot and wrinkle formation in Caucasians and East Asians. Preliminary evidence suggests that at least some of these effects may be mediated via aryl hydrocarbon receptor (AhR ) signaling in human skin.
Following short-term exposure to air pollution from a California wildfire, rates of clinic visits for both atopic dermatitis and itch were significantly increased among adults aged 65 years or older. This finding suggests that the skin of older adults has a greater vulnerability to air pollution, with rapid outcomes after short-term exposure to air pollution. The increased association of risk for pollution-induced skin exacerbations with older age may be due to age-related molecular processes affecting skin barrier function.9
The skin is the most exposed organ to the environment; therefore, cutaneous diseases are inclined to have greater sensitivity to climate. Global warming is responsible for a warm and humid environment which can encourage bacterial and fungal colonization, causing an increased incidence of skin infections. Global warming, deforestation and changes in precipitation are linked to variations in the geographical distribution of vectors of some infectious diseases; i.e., malaria, leishmaniasis and Lyme disease. Additionally, climate change can affect the ozone layer, cloud cover and relative humidity—all regulate the amount of UV radiation that reaches the earth’s surface. More UV radiation increases incidence of melanoma, squamous cell carcinoma and basal cell carcinoma.10
Exposure to cold air causes thermoregulatory reactions like variations of behavior and physiological adjustments to keep thermal balance by either raising metabolic heat production through shivering or reducing heat losses consecutive to peripheral cutaneous vasoconstriction. A strong vasoconstriction can result in a fast reduction in hand and foot skin temperatures. This can damage tactile sensitivity, manual dexterity and muscle contractile features. Significant temperature reduction can also increase pain and sympathetic drive and decline gross motor function.12
Humans are exposed to heavy metal toxicity through consumption of water containing metal. Heavy metals readily bioaccumulate in vegetables and enter through the food chain. Effects of heavy metal toxicity on human ranges from mild eye, nose and skin irritations to organ dysfunction such as cirrhosis, necrosis, low blood pressure, hypertension and gastrointestinal distress. Of course, some heavy metals such as iron, manganese and zinc are required in minute amounts for various biochemical processes. But other heavy metals, such as lead, cadmium and mercury, are of serious threat and considered foreign in the body. For example, water polluted with arsenic can cause cancer of the lungs, liver and bladder. Kidney and lung damage and bone fragility may result when cadmium-containing water is ingested. Exposure to lead can severely damage the brain and kidneys. In children, lead exposure even at very low concentration may hamper learning, cause memory loss, affect attention and response functions, and generally make children aggressive. The chemical form of mercury in the environment is also important in analyzing toxicity. The organic form of mercury, methyl mercury (MeHg) and dimethyl mercury (DMeHg), is known to be more toxic than inorganic mercury.14 Mercury is present in the food chain.
Excessive exposure to UV carries profound health risks, including atrophy, pigmentary changes, wrinkling and malignancy. UV is epidemiologically and molecularly linked to the three most common types of skin cancer—basal cell carcinoma, squamous cell carcinoma and malignant melanoma.
Recent evidence indicates that IR and heat may induce premature skin aging, just like UV radiation. IR exposure of human skin stimulates the expression of MMP-1 and decreases type I procollagen expression in vivo. Acute IR irradiation also increases new, leaky vessel formation and induces inflammatory cellular infiltration. Heat energy, which increases skin temperature, also increases MMP-1, -3 and -12. It modulates elastin and fibrillin synthesis, resulting in the development of solar elastosis. Acute heat shock in human skin stimulates new vessel formation, recruits inflammatory cells and causes oxidative DNA damage.15 Continuous UV radiation exposure induces oxidative stress in epidermal cells, causing cell damage, fat oxidation and cell inflammation.
Blue light is defined as light within the wavelength range of 400-500nm. The sun is the main source of blue light. It is also emitted by electronic devices, including computer monitors, flat-screen televisions, smartphones, tablets and fluorescent light bulbs. Changing lifestyles; i.e, less time spent outdoors and increased use of light-emitting diode and fluorescent lighting, have changed the pattern of blue light exposure in humans. In controlled clinical settings, blue light can be used to treat conditions such as psoriasis, atopic dermatitis and acne. Blue light is capable of producing various effects on the skin, including deleterious direct effects, such as hyper pigmentation and photo aging, and complex indirect effects, such as circadian rhythm modulation.16 When formulating cosmeceuticals, we should focus on products which control exposure or decrease blue light effects.
Life is stressful. To reduce stress, eat well, avoid smoking and alcohol, and practice meditation. They will enhance quality of life and appear of skin. The best skin in the world is found in Asian countries where women have glowing skin through eating right and maintaining healthy life style. Further research should involve fast developing field of clean Ayurveda, an alternative system to bring balance to life. The Ayurvedic market is expected to approach $29 billion by 2030. It includes natural herbs, plant-based medicines and spices and is heralded as an alternate medicine devoid of side effects.
References:
You Are What You Eat
Dietary factors and nutritional supplements certainly influence skin aging. Nutritional deficiencies can cause cutaneous signs such as dermatitis, alopecia and depigmentation. Frequent fast-food consumption is a major health concern since most fast food is rich in glucose, saturated fats, trans fats, simple carbohydrates, glycated proteins and sodium, and devoid of active antioxidants. When glycated proteins are consumed, they are absorbed in the gut with approximately 30% efficiency and circulate through the bloodstream. They are pro-inflammatory and accumulate on nucleic acids, proteins and lipids, promoting such widely diverse diseases as diabetic sequelae, pulmonary fibrosis and neuro-degeneration.1Trans fats found in processed foods like margarine and fast food can clog arteries, which takes away elasticity from the skin. High glycemic index foods such as bread, chips, popcorn and cake are rapidly digested and absorbed which causes rapid spikes in blood sugar levels. These spikes affect biochemical functions like the insulin pathway and may affect blood vessels and accelerate the aging process. High blood sugar levels can affect collagen tissues and make skin vulnerable to lines and wrinkles.
Artificial colors enhance the visual appeal of food and non-food products. Some synthetic colors, like tartrazine, have adverse effects on human health and especially young children. Tartrazine is an artificial lemon-yellow azo dye, recognized as E102 or C.I. 19140 or FD&C Yellow 5 and used for the coloring of food. Tartrazine may be found in nonfood products like soaps, cosmetics, shampoos and other hair products, crayons and stamp dyes. A diversity of immunologic reactions has been recognized in tartrazine consumption, comprising general fatigue, nervousness, migraines, clinical depression, purple skin spots and sleep disruption. Either consumption or cutaneous contact with a material containing tartrazine can produce symptoms of sensitivity.2
Pharmaceuticals are the major part of treatment of various disorders. Drugs can induce or enhance skin diseases such as phototoxicity, skin pigmentation, acne, itching and psoriasis. Drugs can cause hair disorders like alopecia. Penicillin, sulfa, phenyl-butazone and tetracycline are the most common drug inducing various skin disorders.3
Studies have clearly shown varying associations exist between tobacco or alcohol use, and skin photoaging and facial aging. Smoking generates free radicals which, in turn, damage skin repair mechanisms and reduce collagen and elastin synthesis, which leads to premature skin aging. In our studies, we saw a major decline in glutathione peroxidase clearly associated with smoking and alcohol. Smoking can also cause cutaneous micro vascular contraction that increases in relation to the duration and amount of exposure. Research shows alcohol dramatically affects appearance and skin features. Drinking alcohol causes dehydration, depleting skin blood’s capillaries flow. Chronic alcohol consumption has detrimental impacts on skin health, impairing the skin’s antioxidant defense system by decreasing dermal carotenoid concentrations. Alcohol also causes peripheral vasodilation, which can lead to dilated facial capillaries.4
Stress & Skin
The skin and the central nervous system share several neurotransmitters, hormones and receptors. Psychological stressors are known to trigger the immune system and have an influence on both innate and acquired immunity. A number of studies provide clear evidence that psycho-social factors such as depression and anxiety have a serious effect on the outcome of numerous medical conditions, including those of the skin. Psychological factors and stress can lead to skin conditions such as psoriasis, atopic dermatitis, acne, urticaria, pruritus and alopecia.5Clinical observations have suggested that there is an intrinsic connection between psychological state and skin diseases. Chronic psychological stress stimulates the autonomic nervous system, renin-angiotensin system and the hypothalamic-pituitary-adrenal axis. Prolonged activation can result in chronic immune dysfunction, increased reactive oxygen species (ROS) production and DNA damage, which are known contributors to skin aging. Sleep deprivation affects features relating to the eyes, mouth, and skin. The investigators reported drooping eyelids; red, swollen eyes; dark circles under the eyes; pale skin, wrinkles/fine lines, and drooping corners of the mouth.
An analytic cross-section study was conducted on 400 subjects—200 patients with primary psychiatric disorders and 200 age- and sex-matched individuals free from primary psychiatric disorders. Researchers found that infectious skin diseases are the most common skin disease categories in psychiatric patients. Although psychogenic skin disorders occur exclusively in primary psychiatric disorder patients, it is much less frequent than the infectious skin diseases overall.6
An Australian Longitudinal Study, conducted on 6,630 women, highlights that the relationship between skin disease and psychological morbidity in young women. It confirms that psychological morbidity (depression, anxiety and stress) is a factor in the causation of skin disease.7
Chronic diseases are major killers in modern era. Physical inactivity is a primary cause of most chronic diseases. Conversely, physical activity prevents and delays chronic diseases, implying such diseases need not be the outcome of life.
External Factors
Studies show that pollutants gain entrance to the skin by direct accumulation on the skin surface. Absorption via the hair follicles, inhalation, ingestion and circulation of pollutants in plasma penetrate dermal tissues. Pollution creates oxidative stress for skin. Air pollutants enter the skin via nanoparticles and generate quinones; i.e., redox cycling chemicals that produce ROS. This increase in the amount of ROS and free radicals within the cell and its mitochondria overcomes the skin’s innate antioxidant defenses.Most commonly, pollutants are generated through the burning of fossil fuels by vehicles and industries giving rise to components such as particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs). Additional pollutants are derived from a variety of unrelated sources, such as cigarette smoke, ultraviolet (UV) light, volatile organic compounds (VOCs), and tropospheric (ground level) ozone. Particulate pollutants with a diameter of 2.5mm or less (PM2.5) and 10mm or less (PM10) and nano particles are the main constituents of PM. PAHs and VOCs are mainly generated by power plants, industries, vehicles and domestic agricultural sources.8
Epidemiological evidence that exposure to traffic-related air pollution including PM, NOx and ground level ozone is associated with pigment spot and wrinkle formation in Caucasians and East Asians. Preliminary evidence suggests that at least some of these effects may be mediated via aryl hydrocarbon receptor (AhR ) signaling in human skin.
Following short-term exposure to air pollution from a California wildfire, rates of clinic visits for both atopic dermatitis and itch were significantly increased among adults aged 65 years or older. This finding suggests that the skin of older adults has a greater vulnerability to air pollution, with rapid outcomes after short-term exposure to air pollution. The increased association of risk for pollution-induced skin exacerbations with older age may be due to age-related molecular processes affecting skin barrier function.9
The skin is the most exposed organ to the environment; therefore, cutaneous diseases are inclined to have greater sensitivity to climate. Global warming is responsible for a warm and humid environment which can encourage bacterial and fungal colonization, causing an increased incidence of skin infections. Global warming, deforestation and changes in precipitation are linked to variations in the geographical distribution of vectors of some infectious diseases; i.e., malaria, leishmaniasis and Lyme disease. Additionally, climate change can affect the ozone layer, cloud cover and relative humidity—all regulate the amount of UV radiation that reaches the earth’s surface. More UV radiation increases incidence of melanoma, squamous cell carcinoma and basal cell carcinoma.10
Temperature Change
Core body temperatures are almost universally maintained around 37°C and skin temperatures around 35°C. Hyperthermia, elevated core body temperature, occurs when elevated skin temperatures are sustained, which can result in death when core body temperatures reach around 42-43°C. While acclimatization can reduce the burden of heat, acclimatization only improves sweating mechanisms, and the cooling effects of acclimated people have limits. As relative humidity increases, the evaporative cooling effects of sweating decreases. Once relative humidity reaches 100%, sweating continues but evaporative cooling stops. Even acclimated or healthy humans face mortality with prolonged skin temperatures of 37-38°C. Thus, it is reasonable that sustained periods of time with HI > 35°C can be physically intolerable, and outdoor exposure to Wet Bulb Globe Temperature WBGTmax > 30 °C has been associated with increased mortality rates among vulnerable populations.11Exposure to cold air causes thermoregulatory reactions like variations of behavior and physiological adjustments to keep thermal balance by either raising metabolic heat production through shivering or reducing heat losses consecutive to peripheral cutaneous vasoconstriction. A strong vasoconstriction can result in a fast reduction in hand and foot skin temperatures. This can damage tactile sensitivity, manual dexterity and muscle contractile features. Significant temperature reduction can also increase pain and sympathetic drive and decline gross motor function.12
Air & Water Pollutants
Increasing globalization has led to congested metro cities and increased time spent in traffic during routine travel. Increased road traffic affects human health in several ways. Automobile emissions contain toxic chemicals that pollute the atmosphere. Road traffic emissions produce greenhouse gases that contribute to global warming. Vehicles emit a range of pollutants, including nitrogen oxide (NOx) and particulate matter (PM).13Humans are exposed to heavy metal toxicity through consumption of water containing metal. Heavy metals readily bioaccumulate in vegetables and enter through the food chain. Effects of heavy metal toxicity on human ranges from mild eye, nose and skin irritations to organ dysfunction such as cirrhosis, necrosis, low blood pressure, hypertension and gastrointestinal distress. Of course, some heavy metals such as iron, manganese and zinc are required in minute amounts for various biochemical processes. But other heavy metals, such as lead, cadmium and mercury, are of serious threat and considered foreign in the body. For example, water polluted with arsenic can cause cancer of the lungs, liver and bladder. Kidney and lung damage and bone fragility may result when cadmium-containing water is ingested. Exposure to lead can severely damage the brain and kidneys. In children, lead exposure even at very low concentration may hamper learning, cause memory loss, affect attention and response functions, and generally make children aggressive. The chemical form of mercury in the environment is also important in analyzing toxicity. The organic form of mercury, methyl mercury (MeHg) and dimethyl mercury (DMeHg), is known to be more toxic than inorganic mercury.14 Mercury is present in the food chain.
UV & IR Damage
Natural sunlight is polychromatic; therefore, its ultimate effects on the human skin are the result of not only the action of each wavelength separately, but also interactions among the many wavelengths, including UV, visible light and infrared (IR).Excessive exposure to UV carries profound health risks, including atrophy, pigmentary changes, wrinkling and malignancy. UV is epidemiologically and molecularly linked to the three most common types of skin cancer—basal cell carcinoma, squamous cell carcinoma and malignant melanoma.
Recent evidence indicates that IR and heat may induce premature skin aging, just like UV radiation. IR exposure of human skin stimulates the expression of MMP-1 and decreases type I procollagen expression in vivo. Acute IR irradiation also increases new, leaky vessel formation and induces inflammatory cellular infiltration. Heat energy, which increases skin temperature, also increases MMP-1, -3 and -12. It modulates elastin and fibrillin synthesis, resulting in the development of solar elastosis. Acute heat shock in human skin stimulates new vessel formation, recruits inflammatory cells and causes oxidative DNA damage.15 Continuous UV radiation exposure induces oxidative stress in epidermal cells, causing cell damage, fat oxidation and cell inflammation.
Blue light is defined as light within the wavelength range of 400-500nm. The sun is the main source of blue light. It is also emitted by electronic devices, including computer monitors, flat-screen televisions, smartphones, tablets and fluorescent light bulbs. Changing lifestyles; i.e, less time spent outdoors and increased use of light-emitting diode and fluorescent lighting, have changed the pattern of blue light exposure in humans. In controlled clinical settings, blue light can be used to treat conditions such as psoriasis, atopic dermatitis and acne. Blue light is capable of producing various effects on the skin, including deleterious direct effects, such as hyper pigmentation and photo aging, and complex indirect effects, such as circadian rhythm modulation.16 When formulating cosmeceuticals, we should focus on products which control exposure or decrease blue light effects.
Life is stressful. To reduce stress, eat well, avoid smoking and alcohol, and practice meditation. They will enhance quality of life and appear of skin. The best skin in the world is found in Asian countries where women have glowing skin through eating right and maintaining healthy life style. Further research should involve fast developing field of clean Ayurveda, an alternative system to bring balance to life. The Ayurvedic market is expected to approach $29 billion by 2030. It includes natural herbs, plant-based medicines and spices and is heralded as an alternate medicine devoid of side effects.
References:
- Diet, Skin Aging, and Glycation; Zoe Diana Draelos; Cosmetic Dermatology, May 2012, Vol. 25 No. 5
- Toxicological and safety assessment of tartrazine as a synthetic food additive on health biomarkers: A review; Kamal A. Amin and Fawzia S. Al-Shehri ;Afr. J. Biotechnol. Vol. 17(6), pp. 139-149,DOI: 10.5897/AJB2017.16300
- A review on drug induced skin disorders: pathophysiology and therapeutics; Priyanka N., R. Srinivasan; Int J Res Dermatol. 2020 Sep;6(5): 715-722; DOI: http://dx.doi.org/10.18203/issn.2455-4529.IntJResDermatol20203761
- Impact of Smoking and Alcohol Use on Facial Aging in Women: Results of a Large Multinational, Multiracial, Cross-sectional Survey; Greg D. Goodman et Al; Journal of Clinical and Aesthetic Dermatology, August 2019, Vol. 12, No. 8
- The psychiatric aspects of skin disorders; Ossama T Osman et Al; Expert Rev. Dermatol. 6(2), 195-209 (2011); 10.1586/EDM.11.10
- Skin diseases in patients with primary psychiatric conditions: A hospital based study; Abeer M. Kamel et Al; Journal of Epidemiology and Global Health (2013) 3, 131-138; http://dx.doi.org/10.1016/j.jegh.2013.03.005
- The Relationship Between Psychiatric Illnesses and Skin Disease A Longitudinal Analysis of Young Australian Women; Parker Magin, David Sibbritt, Kylie Bailey;ARCH DERMATOL/ VOL 145 (NO. 8), AUG 2009
- Air pollution and skin disorders; Wendy Roberts; International Journal of Women’s Dermatology 7 (2021) 91–97; https://doi.org/10.1016/ j. ijwd.2020.11.001
- Association of Exposure to Wildfire Air Pollution with Exacerbations of Atopic Dermatitis and Itch Among Older Adults; Raj Maria L. Wei et Al; JAMA Network Open. 2022;5(10): e2238594. doi:10.1001/jamanetworkopen.2022.38594
- Effects of climate changes on skin diseases; Matteo Megna et al; Expert Rev. Anti-Infect. Ther. Early online, 1–11 (2014); 10.1586/14787210.2014.875855
- Global urban population exposure to extreme heat Cascade Tuholske et al; PNAS 2021 Vol. 118 No. 41; 2024792118; https://doi.org/10.1073/pnas.2024792118
- The effects of short‐term and long‐term exposure to extreme cold environment on the body’s physiological responses: An experimental study; Keivan Saedpanah1 | Mohsen Aliabadi2 | Majid Motamedzade3 Rostam Golmohammadi; Hum. Factors Man. 2018;1–9.DOI: 10.1002/hfm.20770
- A Study on Road Traffic Pollution and Its Impact on Human Health; Amrapali Jambhulkar1 Shrikant G. Borkar; Public Health Relevance of Road Traffic Injury in India; ISBN: 978-93-89000-62-7; Ch 11
- Water Pollution: Effects, Prevention, and Climatic Impact. Water Challenges of an Urbanizing World [Internet]. 2018 Mar 21; Available from: http://dx.doi.org/10.5772/intechopen.72018
- Effects of Infrared Radiation and Heat on Human Skin Aging in vivo; Soyun Cho et al; Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 15–19; doi:10.1038/jidsymp.2009.7
- Direct and Indirect Effects of Blue Light Exposure on Skin: A Review of Published Literature; Orawan Suitthimeathegorn et Al; Skin Pharmacol Physiol2022;35:305–318 DOI: 10.1159/000526720