Bioactive Compounds for Skin Health: A Review

In the paper

“Retinoids and all biologically active forms of vitamin A also promote the remodeling of reticulin fibers and synthesis of a new capillary network in the dermis.”

What the sources say

• Partly supported

  The “RA delivery systems for skin diseases > RA mode of action” section (page unavailable) says that all-trans retinoic acid (ATRA) induces skin angiogenesis and collagen deposition. That supports the capillary-network claim in broad terms, but the paper does not specify remodeling of reticulin fibers or establish these effects for all biologically active forms of vitamin A. (LLM, conf=0.87)

  cites [35] Ferreira, 2020, Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine, Nat. Commun. sourceExperimental — accuracy not yet measured
• Partly supported

  The paper reports that topical retinol enhanced collagen synthesis in naturally aged skin, supporting a general effect on dermal connective tissue. It does not report remodeling of reticulin fibers or formation of a new capillary network, and its findings do not establish the effect for all biologically active forms of vitamin A. The Results also state that seven days of retinol treatment did not alter the measured connective-tissue abnormalities; page numbers were unavailable in our copy. (LLM, conf=0.86)

  cites [42] Varani, 2000, Vitamin A antagonizes decreased cell growth and elevated collagen degrading matrix metaloproteinases and stimulates collagen accumulation in naturally aged human skin, J. Investig. Dermatol. sourceExperimental — accuracy not yet measured

In the paper

“They exhibit anti-inflammatory, antibacterial, antifungal, antiviral, antiallergic, anticancer and anticoagulant properties [190,191,192,193,197].”

What the sources say

• Partly supported

  The Conclusions and the section on prooxidant activity describe anti-inflammatory and anticancer effects; ‘Other bioactive effects’ reports antibacterial and anti-HIV activity, and ‘Antiallergic activity’ reports effects of apple tannins. Our copy does not establish antifungal or anticoagulant properties. Its reference to inhibition of platelet aggregation does not, by itself, support the broader anticoagulant claim. (LLM, conf=0.88)

  cites [190] Han, 2007, Dietary polyphenols and their biological significance, Int. J. Mol. Sci. sourceExperimental — accuracy not yet measured
• Partly supported

  Section 2.3 identifies anti-inflammatory properties in capsaicinoids, a subgroup of polyphenolic amides. The Introduction and Section 5.1 link polyphenol-rich diets with lower cancer risk, but do not establish anticancer properties for polyphenols generally. The cited passages do not support the antibacterial, antifungal, antiviral, antiallergic, or anticoagulant properties attributed to them. (LLM, conf=0.86)

  cites [191] Tsao, 2010, Chemistry and biochemistry of dietary polyphenols, Nutrients sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction reports antibacterial, antiviral, anti-inflammatory and anti-allergenic activities, while Section 5 describes anticancer effects of some polyphenols. Section 5 also reports antimicrobial and anti-thrombotic effects, but the passages found do not specifically establish antifungal or anticoagulant properties; anti-thrombotic is not synonymous with anticoagulant. Page numbers were not available in our copy. (LLM, conf=0.85)

  cites [192] Shahidi, 2015, Phenolics and polyphenolics in foods, beverages and spices: Antioxidant activity and health effects –A review, J. Funct. Foods sourceExperimental — accuracy not yet measured
• Not checked yetcites [193] Jain, 2010, Flavonoids as nutraceuticals. A review, Herba Pol.
• Partly supported

  The “Polyphenols and skin photoprotection” section describes anti-inflammatory properties and potential prevention of skin cancer; the Conclusion also describes anti-photocarcinogenic effects. Our copy does not support the attributed antibacterial, antifungal, antiviral, antiallergic, or anticoagulant properties. (LLM, conf=0.88)

  cites [197] Nichols, 2010, Skin photoprotection by natural polyphenols: Anti-inflammatory, antioxidant and DNA repair mechanisms, Arch. Dermatol. Res. sourceExperimental — accuracy not yet measured

In the paper

“In the human body, carotenoids mainly accumulate in lipid tissue cells and the liver.”

What the sources say

• Partly supported

  Section 3, “Carotenoids and the Skin” (page unavailable), says systemically applied carotenoids are stored in body fat tissue. It does not say they accumulate in the liver or establish that fat tissue and the liver are their main sites of accumulation in the human body; a search for “liver” found no supporting passage. (LLM, conf=0.88)

  cites [220] Balić, A., and Mokos, M. (2019). Do we utilize our knowledge of the skin protective effects of carotenoids enough?. Antioxidants, 8. sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction (page unavailable) identifies adipose tissue as one source from which carotenoids reach the epidermis. It does not say that carotenoids accumulate mainly in adipose tissue cells or the liver; the paper’s distribution discussion concerns skin. (LLM, conf=0.73)

  cites [229] Darvin, 2011, The role of carotenoids in human skin, Molecules sourceExperimental — accuracy not yet measured

In the paper

“A balanced diet plays an important role in the proper functioning of the human body, including the skin.”

What the sources say

• Not checked yetcites [14] Kaimal, 2010, Diet in dermatology: Revisited, IndianJ. Dermatol. Venereol. Leprol. source
• Not checked yetcites [15] Boelsma, 2003, Human skin condition and its associations with nutrient concentrations in serum and diet, Am. J. Clin. Nutr. source
• Not checked yetcites [16] Divya, 2015, Role of diet in dermatological conditions, J. Nutr. Food Sci.
• Not checked yetcites [17] Navratil, 2014, The impact of diet on common skin disorders, J. Nutr. Ther. source

In the paper

“One of the most common dermatological and cosmetic concerns is skin ageing: a natural, complex process influenced by two mechanisms—intrinsic (genetic, chronological) ageing resulting from the passage of time, and extrinsic ageing (photoaging), caused by environmental factors (including UV radiation, environmental pollution and cigarette smoke) [5,6,7,8].”

What the sources say

• Not checked yetcites [5] Bauer, 2014, Reactive molecule species and antioxidative mechanisms in normal skin and skin aging, Skin Pharmacol. Physiol. source
• Not checked yetcites [6] Dahmane, 2012, Intrinsic skin aging: The role of oxidative stress, Acta Dermatovener.
• Not checked yetcites [7] Nishigori, 2003, Photoaging and oxidative stress, Exp. Dermatol. source
• Not checked yetcites [8] Binic, I., Lazarevic, V., Ljubenovic, M., Mojsa, J., and Sokolovic, D. (2013). Skin ageing: Natural weapons and strategies. Evid. Based Complement. Alternat. Med. source

In the paper

“The two processes overlap and are closely linked to increased reactive oxygen species (ROS) and oxidative stress in the skin [9].”

What the sources say

• Not checked yetcites [9] Poljšak, B., and Dahmane, R.G. (2012). Free radicals and extrinsic skin aging. Dermatol. Res. Pract., 1–10. source

In the paper

“Moreover, vitamin A promotes the compaction of the stratum corneum and deposition of GAGs in the stratum corneum and intercellular spaces in the epidermis [40].”

What the sources say

• Not checked yetcites [40] Bagatin, 2009, Cosmeceuticals vitamins, Clin. Dermatol. source

In the paper

“A study conducted by Kang et al. showed that the application of all-trans-retinol on normal human skin induced epidermal thickening and increased the mRNA expression of cellular retinoic acid binding protein and cellular retinol binding protein [41].”

What the sources say

• Not checked yetcites [41] Kang, 1995, Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation, J. Investig. Dermatol. source

In the paper

“Retinoids are a group of chemical compounds that inhibit cell division during excessive proliferation and activate it when the process is too slow.”

What the sources say

• Not checked yetcites [28] Sorg, 2005, Proposed mechanisms of action for retinoid derivatives in the treatment of skin aging, J. Cosmetic. Dermato. source
• Not checked yetcites [34] Oliveira, L.M., Teixeira, F.M.E., and Sato, M. (2018). N Impact of retinoic acid on immune cells and inflammatory diseases. Mediat. Inflamm. source
• Not checked yetcites [37] Chaudhuri, 2014, Bakuchiol: A retinol-like functional compound revealed by gene expression profiling and clinically proven to have anti-aging effects, Int. J. Cosmet. Sci. source

In the paper

“Retinoids protect collagen against the destruction induced by MMPs, as well as enhancing the synthesis of tissue inhibitors of metalloproteinases (TIMPs) [32,42].”

What the sources say

• Not checked yetcites [32] Zasada, 2019, Retinoids: Active molecules influencing skin structure formation in cosmetic and dermatological treatments, Postepy Dermatol. Alergol. source
• Not checked yetcites [42] Varani, 2000, Vitamin A antagonizes decreased cell growth and elevated collagen degrading matrix metaloproteinases and stimulates collagen accumulation in naturally aged human skin, J. Investig. Dermatol. source

In the paper

“A study in mice by Törmä et al. showed that retinol esters accounted for 90% of the vitamin A in the epidermis, with retinol making up the remaining 10% [39].”

What the sources say

• Not checked yetcites [39] Brunnberg, 1987, Age-related variations in acyl-CoA: Retinol acyltransferase activity and vitamin A concentration in the liver and epidermis of hairless mice, Biochim. Biophys. Acta. source

In the paper

“Retinoids also affect the thickness and color of the skin, regulate the function of the sebaceous glands, and limit sebum production, as well as being responsible for hair and nail growth, and also influencing the distribution of melanin in the skin [27,30,35].”

What the sources say

• Not checked yetcites [27] Khali, 2017, Retinoids: A journey from the molecular structures and mechanisms of action to clinical uses in dermatology and adverse effects, J. Dermatolog. Treat. source
• Not checked yetcites [30] Polcz, 2019, The Role of Vitamin A in Wound Healing, Nutr. Clin. Pract. source
• Not checked yetcites [35] Ferreira, 2020, Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine, Nat. Commun. source

In the paper

“Topical retinol improves the dermal extracellular matrix (ECM) microenvironment (type I collagen, fibronectin, and elastin) and activates ECM-producing cells in aged skin [32,38].”

What the sources say

• Not checked yetcites [32] Zasada, 2019, Retinoids: Active molecules influencing skin structure formation in cosmetic and dermatological treatments, Postepy Dermatol. Alergol. source
• Not checked yetcites [38] Shao, 2017, Molecular basis of retinol anti-ageing properties in naturally aged human skin in vivo, Int. J. Cosmet. Sci. source

In the paper

“This process influences the condition of the connective tissue of the dermis, improving its firmness, hydration and elasticity [35,42].”

What the sources say

• Not checked yetcites [35] Ferreira, 2020, Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine, Nat. Commun. source
• Not checked yetcites [42] Varani, 2000, Vitamin A antagonizes decreased cell growth and elevated collagen degrading matrix metaloproteinases and stimulates collagen accumulation in naturally aged human skin, J. Investig. Dermatol. source

In the paper

“Although the direct antioxidant protection provided by vitamin C is limited to aqueous compartments, vitamin C significantly curtails lipid oxidation by regenerating fat-soluble vitamin E; it regenerates α-tocopherol from α-tocopherol radicals found in cell membranes and lipoproteins [60].”

What the sources say

• Not checked yetcites [60] Jones, 1995, Impact of nutrients on cellular lipid peroxidation and antioxidant defense system, Fundam. Appl. Toxicol. source

In the paper

“The vitamin has been shown to enhance keratinocyte differentiation, reduce differentiation-dependent oxidative stress and maintain the integrity of the skin barrier, which in turn helps to prevent water loss from the skin [55,57].”

What the sources say

• Not checked yetcites [55] Ponec, 1997, The formation of competent barrier lipids in reconstructed human epidermis requires the presence of vitamin C, J. Investig. Dermatol. source
• Not checked yetcites [57] Savini, 2002, Characterization of keratinocyte differentiation induced by ascorbic acid: Protein kinase C involvement and vitamin C homeostasis, J. Investig. Derm. source

In the paper

“Savini et al., in an in vitro study on normal human epidermal keratinocytes, showed that ascorbate improves the barrier functions of the epidermis and promotes the formation of the cornified cell envelope, a specialized structure that protects the body against harmful chemical and physical factors [57].”

What the sources say

• Not checked yetcites [57] Savini, 2002, Characterization of keratinocyte differentiation induced by ascorbic acid: Protein kinase C involvement and vitamin C homeostasis, J. Investig. Derm. source

In the paper

“Retinoids influence the function of melanocytes and the distribution of melanin in the skin, as well as blocking the transport of melanin to epidermal cells.”

What the sources say

• Not checked yetcites [32] Zasada, 2019, Retinoids: Active molecules influencing skin structure formation in cosmetic and dermatological treatments, Postepy Dermatol. Alergol. source

In the paper

“Vitamin C promotes the formation of the epidermal barrier and collagen in the dermis, protects against skin oxidation, helps to counteract skin ageing, and plays a role in the signaling pathways of cell growth and differentiation, which are linked to the occurrence of various skin diseases [55,56].”

What the sources say

• Not checked yetcites [55] Ponec, 1997, The formation of competent barrier lipids in reconstructed human epidermis requires the presence of vitamin C, J. Investig. Dermatol. source
• Not checked yetcites [56] Wang, 2018, Role of Vitamin C in Skin Diseases, Front. Physiol. source

In the paper

“The results clearly indicate that retinyl esters present in the epidermis have strong antiphotocarcinogenic properties and protect DNA against damage by UV radiation [44].”

What the sources say

• Not checked yetcites [44] Antille, 2003, Vitamin A exerts a photoprotective action in skin by absorbing ultraviolet B radiation, J. Investig. Dermatol. source

In the paper

“It functions as a cofactor of proline and lysine hydroxylases, which are responsible for the tertiary structure of collagen; promotes the expression of collagen genes; and activates the production of collagen mRNA by fibroblasts [50].”

What the sources say

• Not checked yetcites [50] Rhie, 2001, Aging-and photoaging-dependent changes of enzymic and nonenzymic antioxidants in the epidermis and dermis of human skin in vivo, J. Investig. Dermatol. source

In the paper

“Varani et al. observed that topical vitamin A (retinol) reduced MMP expression and increased fibroblast growth and collagen synthesis in naturally aged, as it did in photoaged, skin [42].”

What the sources say

• Not checked yetcites [42] Varani, 2000, Vitamin A antagonizes decreased cell growth and elevated collagen degrading matrix metaloproteinases and stimulates collagen accumulation in naturally aged human skin, J. Investig. Dermatol. source

In the paper

“There is scientific evidence that ascorbic acid plays an active role in the proliferation and migration of skin fibroblasts and stimulates the production of collagen and elastin in cultures of fibroblasts [46,49].”

What the sources say

• Not checked yetcites [46] 2009, An overview of ascorbic acid biochemistry, J. Fac. Pharm. Ankara.
• Not checked yetcites [49] Pullar, 2017, The roles of vitamin C in skin health, Nutrients source

In the paper

“Pasonen-Seppanen et al. showed that vitamin C enhanced the differentiation of rat epidermal keratinocytes cell line in an organotypic culture model, resulting in a stronger stratum corneum, which indicates that it has a skin-protective function [58].”

What the sources say

• Not checked yetcites [58] Suhonen, 2001, Vitamin C enhances differentiation of a continuous keratinocyte cell line (REK) into epidermis with normal stratum corneum ultrastructure and functional permeability barrier, Histochem. Cell Biol. source

In the paper

“A review of the literature indicates that vitamin C inhibits melanogenesis with low cytotoxicity, although some studies suggest that the role of vitamin C in inhibiting melanogenesis is very minor [67,68,69].”

What the sources say

• Not checked yetcites [67] Panich, 2011, Inhibition of UVA-mediated Melanogenesis by Ascorbic Acid through Modulation of Antioxidant Defense and Nitric Oxide System, Arch. Pharm. Res. source
• Not checked yetcites [68] Choi, 2010, Effects of vitamin C vs. multivitamin on melanogenesis: Comparative study in vitro and in vivo, Int. J. Dermatol. source
• Not checked yetcites [69] Shimada, 2009, Effects of ascorbic acid on gingival melanin pigmentation in vitro and in vivo, J. Periodontol. source

In the paper

“Supplementation with vitamin C enhances the production of GAGs, promotes the expression of genes coding for antioxidant enzymes and enzymes involved in DNA repair, and inhibits the production of pro-inflammatory cytokines and apoptosis induced by UV radiation or other harmful environmental factors [49].”

What the sources say

• Not checked yetcites [49] Pullar, 2017, The roles of vitamin C in skin health, Nutrients source

In the paper

“However, some researchers have demonstrated that supplementation with Se does not significantly affect the incidence of BCC or is ineffective in preventing it [95,96].”

What the sources say

• Not checked yetcites [95] Combos, 1997, Reduction of cancer mortality and incidence by selenium supplementation, Med Klin source
• Not checked yetcites [96] Slate, 2003, Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial, J. Natl. Cancer. Inst. source

In the paper

“Alpha-tocopherol has been shown to decrease the amount of 8-hydroxydeoxyguanosine produced indirectly by reactive oxygen species, so it may reduce ROS-induced DNA damage and thereby help to retard the development of skin cancer [81].”

What the sources say

• Not checked yetcites [81] Ichihashi, 1999, The inhibitory effect of DL-alpha-tocopheryl ferulate in lecithin on melanogenesis, Anticancer Res.

In the paper

“Research by Pols et al. indicates that a high serum concentration of selenium is associated with an approximately 60% decrease in the incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin [94].”

What the sources say

• Not checked yetcites [94] Heinen, 2009, Serum antioxidants and skin cancer risk: An 8-year community-based follow-up study, Cancer Epidemiol. Biomark. Prev. source

In the paper

“Kim et al. showed that a selenium-rich tuna heart extract enhanced collagen synthesis and promoted the proliferation of skin fibroblasts, thus having anti-ageing and anti-wrinkle effects [93].”

What the sources say

• Not checked yetcites [93] Kim, 2016, Anti-wrinkle effects of a tuna heart H2O fraction on Hs27 human fibroblasts, Int. J. Mol. Med. source

In the paper

“Selenium (Se) is one of the most important trace elements without which the body cannot function properly.”

What the sources say

• Not checked yetcites [88] Bao, 2011, Selenium in human health and disease, Antioxid. Redox Signal. source

In the paper

“It occurs in two forms: inorganic (selenates and selenites) and organic (selenomethionine and selenocysteine) [88].”

What the sources say

• Not checked yetcites [88] Bao, 2011, Selenium in human health and disease, Antioxid. Redox Signal. source

In the paper

“Ichihashi et al., in an in vitro study using cultured human melanoma cells and normal human melanocytes, showed that alpha-tocopherol inhibits tyrosine hydroxylase activity and suppresses melanogenesis [81].”

What the sources say

• Not checked yetcites [81] Ichihashi, 1999, The inhibitory effect of DL-alpha-tocopheryl ferulate in lecithin on melanogenesis, Anticancer Res.

In the paper

“Some research also indicates that vitamin E displays strong photoprotective, firming, hydrating and anti-ageing properties, as well as improving the elasticity, structure and softness of the epidermis and dermis [40,82].”

What the sources say

• Not checked yetcites [40] Bagatin, 2009, Cosmeceuticals vitamins, Clin. Dermatol. source
• Not checked yetcites [82] Keen, 2016, Vitamin E in dermatology, Indian. Dermatol. Online J. source

In the paper

“Furthermore, a combination of vitamin C and other vitamins, including vitamin E, is more effective at reducing melanin than vitamin C alone and can be used for treating skin discoloration, e.g., age spots or melasma [50,68].”

What the sources say

• Not checked yetcites [50] Rhie, 2001, Aging-and photoaging-dependent changes of enzymic and nonenzymic antioxidants in the epidermis and dermis of human skin in vivo, J. Investig. Dermatol. source
• Not checked yetcites [68] Choi, 2010, Effects of vitamin C vs. multivitamin on melanogenesis: Comparative study in vitro and in vivo, Int. J. Dermatol. source

In the paper

“Owing to the antioxidant properties of vitamin E and its ability to scavenge free radicals and become part of lipid structures, it protects against lipid peroxidation and slows skin ageing [80].”

What the sources say

• Not checked yetcites [80] Lee, G.Y., and Han, S.N. (2018). The role of Vitamin E in Immunity. Nutrients, 10. source

In the paper

“The skin is the third most Zn-abundant tissue in the body, with greater amounts in the epidermis than in the dermis [99,102].”

What the sources say

• Not checked yetcites [99] Ogawa, Y., Kinoshita, M., Shimada, S., and Kawamura, T. (2018). Zinc and skin disorders. Nutrients, 10. source
• Not checked yetcites [102] Michaelsson, 1980, Zinc in epidermis and dermis in healthy subjects, Acta Derm. Venereol. source

In the paper

“Selenium supplementation is an important strategy for inhibiting wrinkles, because it can reverse ultraviolet light damage and play an anti-ageing role in the skin [89,92].”

What the sources say

• Not checked yetcites [89] Cai, 2019, Selenium, aging and aging-related diseases, Aging Clin. Exp. Res. source
• Not checked yetcites [92] Favrot, C., Beal, D., Blouin, E., Leccia, M.E., and Roussel, A.M. (2018). Age-dependent protective effect of selenium against UVA irradiation in primary human keratinocytes and the associated DNA repair signature. Oxid. Med. Cell. Longev. source

In the paper

“Zinc (Zn) is an essential microelement with an important role in many physiological processes [97].”

What the sources say

• Not checked yetcites [97] Devi, 2014, Zinc in human health, IOSR-JDMS source

In the paper

“Selenium exhibits strong antioxidant properties and protects against DNA damage [88,89].”

What the sources say

• Not checked yetcites [88] Bao, 2011, Selenium in human health and disease, Antioxid. Redox Signal. source
• Not checked yetcites [89] Cai, 2019, Selenium, aging and aging-related diseases, Aging Clin. Exp. Res. source

In the paper

“Favrot et al. showed that low doses of Se (30 nM) provide potent protection against UVA-induced cytotoxicity in young keratinocytes (from 20–30-year-old donors), while higher concentrations (240 nM) were required for protective efficacy in old keratinocytes (from donors 60–70 years old) [92].”

What the sources say

• Not checked yetcites [92] Favrot, C., Beal, D., Blouin, E., Leccia, M.E., and Roussel, A.M. (2018). Age-dependent protective effect of selenium against UVA irradiation in primary human keratinocytes and the associated DNA repair signature. Oxid. Med. Cell. Longev. source

In the paper

“It is thought that vitamin E, incorporated into the intercellular cement and lipid structures, protects the skin against solar UVB radiation and, thus, against redness and swelling.”

What the sources say

• Not checked yetcites [40] Bagatin, 2009, Cosmeceuticals vitamins, Clin. Dermatol. source
• Not checked yetcites [83] Dahiaya, 2006, Cosmeceuticals: A review of their use for aging and photoaged skin, Cosmet. Dermatol.

In the paper

“The available literature concerning the efficacy of the systemic and topical use of vitamin E is extensive, but the results are often contradictory and range from an improvement in skin appearance to no effect at all [40].”

What the sources say

• Not checked yetcites [40] Bagatin, 2009, Cosmeceuticals vitamins, Clin. Dermatol. source

In the paper

“Selenium should be supplied to the human body with foods of plant and animal origin [26,88] (Table 1).”

What the sources say

• Not checked yetcites [26] Godswill, 2020, Health benefits of micronutrients (vitamins and minerals) and their associated deficiency diseases: A systematic review, Int. J. Food. Sci.
• Not checked yetcites [88] Bao, 2011, Selenium in human health and disease, Antioxid. Redox Signal. source

In the paper

“The mineral is also important for skin function, having a protective effect and the ability to scavenge free radicals [89].”

What the sources say

• Not checked yetcites [89] Cai, 2019, Selenium, aging and aging-related diseases, Aging Clin. Exp. Res. source

In the paper

“Zinc also affects the immune function of the skin, modulating macrophage and neutrophil functions, phagocytic activity and various inflammatory cytokines [98,99].”

What the sources say

• Not checked yetcites [98] Gupta, M., Mahajan, V.K., Mehta, K.S., and Chauhan, P.S. Zinc therapy in dermatology: A review. Dermatol. Res. Pract., 2014. source
• Not checked yetcites [99] Ogawa, Y., Kinoshita, M., Shimada, S., and Kawamura, T. (2018). Zinc and skin disorders. Nutrients, 10. source

In the paper

“It stabilizes skin cell membranes and participates in basal cell mitosis and differentiation [106], while also playing crucial roles in the survival of keratinocytes.”

What the sources say

• Not checked yetcites [106] Vollmer, D.L., West, V.A., and Lephart, E.D. (2018). Enhancing skin health: By oral administration of natural compounds and minerals with implications to the dermal microbiome. Int. J. Mol. Sci., 19. source

In the paper

“Copper ions reduce the risk of the fungal and bacterial infection of minor wounds and cuts, as well as enhancing wound healing [118].”

What the sources say

• Not checked yetcites [118] Borkow, 2014, Using Copper to Improve the Well-Being of the Skin, Curr. Chem. Biol. source

In the paper

“Copper ions are commonly included in cosmetics. Cu is used as an active component of face creams, including those for the care of mature, tired, dull or oily skin [118,130].”

What the sources say

• Not checked yetcites [118] Borkow, 2014, Using Copper to Improve the Well-Being of the Skin, Curr. Chem. Biol. source
• Not checked yetcites [130] Pickart, L., and Margolina, A. (2018). Skin regenerative and anti-cancer actions of copper peptides. Cosmetics, 5. source

In the paper

“It is a cofactor of superoxide dismutase (SOD), an enzyme involved in protecting the skin against the harmful effects of free radicals, and also prevents oxidative damage to cell membranes and lipid peroxidation [118,126].”

What the sources say

• Not checked yetcites [118] Borkow, 2014, Using Copper to Improve the Well-Being of the Skin, Curr. Chem. Biol. source
• Not checked yetcites [126] Philips, 2010, Stimulation of cell proliferation and expression of matrix metalloproteinase-1 and interluekin-8 genes in dermal fibroblasts by copper, Connect. Tissue Res. source

In the paper

“actinic keratoses (a 25% zinc sulphate solution applied topically twice daily for 12 weeks was safe and effective, especially in patients with multiple actinic keratosis lesions) [113]”

What the sources say

• Not checked yetcites [113] Sharquie, 2012, Topical zinc sulphate (25%) solution: A new therapy for actinic keratosis, J. Cutan. Aesthet. Surg. source

In the paper

“Cu stimulates the proliferation of dermal fibroblasts and is involved in the synthesis and stabilization of extracellular matrix skin proteins and angiogenesis.”

What the sources say

• Not checked yetcites [118] Borkow, 2014, Using Copper to Improve the Well-Being of the Skin, Curr. Chem. Biol. source
• Not checked yetcites [126] Philips, 2010, Stimulation of cell proliferation and expression of matrix metalloproteinase-1 and interluekin-8 genes in dermal fibroblasts by copper, Connect. Tissue Res. source

In the paper

“Zinc preparations in the form of pastes or ointments cleanse the skin of excess sebum, restore its natural pH, and have astringent, anti-inflammatory and anti-acne effects.”

What the sources say

• Not checked yetcites [97] Devi, 2014, Zinc in human health, IOSR-JDMS source
• Not checked yetcites [98] Gupta, M., Mahajan, V.K., Mehta, K.S., and Chauhan, P.S. Zinc therapy in dermatology: A review. Dermatol. Res. Pract., 2014. source
• Not checked yetcites [99] Ogawa, Y., Kinoshita, M., Shimada, S., and Kawamura, T. (2018). Zinc and skin disorders. Nutrients, 10. source
• Not checked yetcites [107] Nitzan, 2006, Zinc in skin pathology and care, J. Dermatolog. Treat. source
• Not checked yetcites [110] Kim, 2014, Hair zinc levels and the efficacy of oral zinc supplementation in patients with atopic dermatitis, Acta Derm. Venereol. source

In the paper

“Copper deficiency reduces the activity of the enzyme Cu/Zn-SOD and ceruloplasmin, as well as copper-independent enzymes, including catalase and glutathione peroxidase.”

What the sources say

• Not checked yetcites [127] Milewska, 2016, Trace elements as an activator of antioxidant enzymes, Postepy. Hig. Med. Dosw. source

In the paper

“xeroderma pigmentosum (a 20% topical application of a zinc sulphate solution for 4 months to 2 years improved all types of skin lesions, softened the skin, lightened the skin color, and cleared the skin of solar keratosis and small malignancies) [114]”

What the sources say

• Not checked yetcites [114] Sharquie, 2008, Topical therapy of xeroderma pigmentosa with 20% zinc sulfate solution, IASJ

In the paper

“It plays an important role in preventing the damage induced by UV radiation, influences collagen metabolism, exhibits antiandrogen properties by modulating the activity of type 1 and 2 5α-reductase, and also promotes lipogenesis and glucose transport through insulin-like effects on 3T3-L1 fibroblasts and adipocytes [98,107,108].”

What the sources say

• Not checked yetcites [98] Gupta, M., Mahajan, V.K., Mehta, K.S., and Chauhan, P.S. Zinc therapy in dermatology: A review. Dermatol. Res. Pract., 2014. source
• Not checked yetcites [107] Nitzan, 2006, Zinc in skin pathology and care, J. Dermatolog. Treat. source
• Not checked yetcites [108] Tang, 2001, Zinc has an insulin-like effect on glucose transport mediated by phosphoinositol-3-kinaseand Akt in 3T3-L1 fibroblasts and adipocytes, J. Nutr. source

In the paper

“Zinc oxide, due to its ability to reflect and disperse UV rays, is used as a physical filter in sunscreens [97,98,99,107,110].”

What the sources say

• Not checked yetcites [97] Devi, 2014, Zinc in human health, IOSR-JDMS source
• Not checked yetcites [98] Gupta, M., Mahajan, V.K., Mehta, K.S., and Chauhan, P.S. Zinc therapy in dermatology: A review. Dermatol. Res. Pract., 2014. source
• Not checked yetcites [99] Ogawa, Y., Kinoshita, M., Shimada, S., and Kawamura, T. (2018). Zinc and skin disorders. Nutrients, 10. source
• Not checked yetcites [107] Nitzan, 2006, Zinc in skin pathology and care, J. Dermatolog. Treat. source
• Not checked yetcites [110] Kim, 2014, Hair zinc levels and the efficacy of oral zinc supplementation in patients with atopic dermatitis, Acta Derm. Venereol. source

In the paper

“Furthermore, Cu is a cofactor of tyrosinase, the main enzyme involved in synthesis of the skin pigment melanin [128].”

What the sources say

• Not checked yetcites [128] Olivares, 2009, New insights into the active site structure and catalytic mechanism of tyrosinase and its related proteins, Pigment Cell Melanoma Res. source

In the paper

“EFAs have therapeutic properties (e.g., anti-inflammatory and anti-allergic) and exert protective effects.”

What the sources say

• Not checked yetcites [156] Michalak, 2018, Oils from fruit seeds and their dietetic and cosmetic significance, Herba Pol. source
• Not checked yetcites [157] Burris, 2013, Acne: The role of medical nutrition therapy, J. Acad. Nutr. Diet. source

In the paper

“In comparison with other metal compounds, copper has a low allergenic potential, and the risk of adverse side effects due to skin contact with the metal is small [132,133].”

What the sources say

• Not checked yetcites [132] Hostynek, 2003, Copper hypersensitivity: Dermatologic aspects-an overview, Rev. Environ. Health source
• Not checked yetcites [133] Fage, 2014, Copper hypersensitivity, Contact Dermat. source

In the paper

“Silicone elastomeric particles can absorb various liquids, including emollients and sebum, and can thus be used as an agent to carry active ingredients to the skin or to control sebum deposition in the skin [136,142].”

What the sources say

• Not checked yetcites [136] Harlim, 2018, Silicon level in skin tissues of normal female individuals, J. Pakistan Assoc. Dermatologists.
• Not checked yetcites [142] Nair, 2013, Basic considerations in the dermatokinetics of topical formulations, Bras. J. Pharmaceut. Sci.

In the paper

“The symptoms of fatty acid deficiency include dryness of the epidermis, peeling, flabby skin, skin inflammation, an increased susceptibility to irritation and slower healing.”

What the sources say

• Not checked yetcites [153] Correa, 2014, Molecular interactions of plant oil components with stratum corneum lipids correlate with clinical measures of skin barrier function, Exp. Dermatol. source
• Not checked yetcites [154] Feingold, 2014, Role of lipids in the formation and maintenance of the cutaneous permeability barier, Biochim. Biophys. Acta. source
• Not checked yetcites [158] Cakir, 2004, Essential oil and fatty acid composition of the fruits of Hippophae rhamnoides L. (Sea Buckthorn) and Myrtus communis L. from Turkey, Biochem. Syst. Ecol. source
• Not checked yetcites [159] Janssens, 2014, The important role of stratum corneum lipids for the cutaneous barrier function, Biochim. Biophys. Acta. source

In the paper

“A deficiency of essential fatty acids can also reduce the fluidity of sebum, which leads to the obstruction of the sebaceous glands and the appearance of blackheads and inflammation [152,157].”

What the sources say

• Not checked yetcites [152] Michalak, 2018, Plant oils in cosmetology and dermatology, Pol. J. Cosmetol.
• Not checked yetcites [157] Burris, 2013, Acne: The role of medical nutrition therapy, J. Acad. Nutr. Diet. source

In the paper

“Treatment with silicon may also improve keratin structure in the hair and nails and reduce brittleness [138].”

What the sources say

• Not checked yetcites [138] Barel, 2005, Effect of oral intake of choline-stabilized orthosilicic acid on skin, nails and hair in women with photodamaged skin, Arch. Dermatol. Res. source

In the paper

“GLA applied topically as a cream penetrates to the stratum corneum, while taken orally, it reaches the dermis, enhancing its cohesiveness and preventing excessive TEWL [156,157].”

What the sources say

• Not checked yetcites [156] Michalak, 2018, Oils from fruit seeds and their dietetic and cosmetic significance, Herba Pol. source
• Not checked yetcites [157] Burris, 2013, Acne: The role of medical nutrition therapy, J. Acad. Nutr. Diet. source

In the paper

“Ferreira et al. investigated the oral intake of two forms of Si—maltodextrin-stabilized orthosilicic acid (M-OSA) and monomethylsilanetriol (MMST)—and their effects on the nails, skin and hair. They were found to improve skin parameters, increase eyelash length, reduce facial wrinkles and UV spots, and act as aluminum detoxification agents [135].”

What the sources say

• Not checked yetcites [135] Ferreira, A.O., Freire, É.S., Polonini, H.C., da Silva, P.J.L.C., Brandão, M.A.F., and Raposo, N.R.B. (2018). Anti-aging effects of monomethylsilanetriol and maltodextrin-stabilized orthosilicic acid on nails, skin and hair. Cosmetics, 5. source

In the paper

“The copper tripeptide complex (GHK-Cu and GSH-Cu) plays an important role in the protection and regeneration of skin tissue, increases the synthesis of collagen and elastin, and improves the condition of ageing skin.”

What the sources say

• Not checked yetcites [130] Pickart, L., and Margolina, A. (2018). Skin regenerative and anti-cancer actions of copper peptides. Cosmetics, 5. source

In the paper

“Owing to unsaturated fatty acids, which, alongside ceramides and cholesterol, are components of the intracellular cement, the skin can act as an effective barrier limiting TEWL, thus ensuring adequate hydration and protecting against external factors [153,154,156].”

What the sources say

• Not checked yetcites [153] Correa, 2014, Molecular interactions of plant oil components with stratum corneum lipids correlate with clinical measures of skin barrier function, Exp. Dermatol. source
• Not checked yetcites [154] Feingold, 2014, Role of lipids in the formation and maintenance of the cutaneous permeability barier, Biochim. Biophys. Acta. source
• Not checked yetcites [156] Michalak, 2018, Oils from fruit seeds and their dietetic and cosmetic significance, Herba Pol. source

In the paper

“Si also promotes the synthesis of elastin and GAGs, helps to preserve blood vessel elasticity, and increases the resistance and thickness of nail and hair fibers [135].”

What the sources say

• Not checked yetcites [135] Ferreira, A.O., Freire, É.S., Polonini, H.C., da Silva, P.J.L.C., Brandão, M.A.F., and Raposo, N.R.B. (2018). Anti-aging effects of monomethylsilanetriol and maltodextrin-stabilized orthosilicic acid on nails, skin and hair. Cosmetics, 5. source

In the paper

“In a group of 50 women with photodamaged facial skin taking 10 mg of Si/day orally for 20 weeks, significant improvements were observed in the surface characteristics and mechanical properties of the skin, as was a positive effect on the brittleness of the hair and nails [138].”

What the sources say

• Not checked yetcites [138] Barel, 2005, Effect of oral intake of choline-stabilized orthosilicic acid on skin, nails and hair in women with photodamaged skin, Arch. Dermatol. Res. source

In the paper

“Silicones are included in cosmetic formulations such as hair conditioners and shampoos to give hair a silky appearance and shine, as well as in facial creams to protect and improve the skin’s strength and elasticity [134,136].”

What the sources say

• Not checked yetcites [134] Addor, 2016, Use of silicon for skin and hair care: An approach of chemical forms available and efficacy, An. Bras. Dermatol. source
• Not checked yetcites [136] Harlim, 2018, Silicon level in skin tissues of normal female individuals, J. Pakistan Assoc. Dermatologists.

In the paper

“Organic silicon plays an important role in skin structure, promotes neocollagenesis, strengthens connective tissue, and reduces the risk of alopecia [139].”

What the sources say

• Not checked yetcites [139] Mancinella, 1991, Silicon, a trace element essential for living organisms. Recent knowledge on its preventive role in atherosclerotic process, aging and neoplasms, Clin. Ter.

In the paper

“Furthermore, the supplementation of diets with vegetable or fish oils may generate local cutaneous anti-inflammatory metabolites, which could serve as adjuncts in the management of skin inflammatory disorders [185].”

What the sources say

• Not checked yetcites [185] Ziboh, 1996, The significance of polyunsaturated fatty acids in cutaneous biology, Lipids source

In the paper

“The study showed that a 10-week administration of the antioxidants to hairless mice irradiated three times a week with UVB radiation significantly prevented the UVB-induced expression of MMPs and mitogen-activated protein (MAP) kinase, as well as the activation of the transcription factor AP-1.”

What the sources say

• Not checked yetcites [203] Cho, 2007, Anti-wrinkling effects of the mixture of vitamin C, vitamin E, pycnogenol and evening primrose oil, and molecular mechanisms on hairless mouse skin caused by chronic ultraviolet B irradiation, Photodermatol. Photoimmunol. Photomed source

In the paper

“There are studies indicating that fish oils have a protective role and can reduce the severity of erythema.”

What the sources say

• Not checked yetcites [186] Rhodes, 1994, Dietary fish-oil supplementation in humans reduces UVB-erythemal sensitivity but increases epidermal lipid peroxidation, J. Investig. Derm. source
• Not checked yetcites [187] Rhodes, 2003, Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers, Carcinogenesis source

In the paper

“Research has confirmed the photochemoprotective, antioxidant, anti-inflammatory and antiproliferative properties of pomegranate extract.”

What the sources say

• Not checked yetcites [208] Afaq, 2005, Anthocyanin- and hydrolyzable tannin-rich pomegranate fruit extract modulates MAPK and NF-kappa B pathways and inhibits skin tumorigenesis in CD-1 mice, Int. J. Cancer source
• Not checked yetcites [209] Khan, 2012, Pomegranate fruit extract inhibits UVB-induced inflammation and proliferation by modulating NF-κB and MAPK signaling pathways in mouse skin, Photochem. Photobiol. source
• Not checked yetcites [210] Kasai, 2006, Effects of oral administration of ellagic acid-rich pomegranate extract on ultraviolet-induced pigmentation in the human skin, J. Nutr. Sci. Vitaminol. source

In the paper

“Furthermore, they soothe irritation and reduce the redness of skin, accelerating the natural regeneration of the epidermis, stabilizing the capillaries, improving microcirculation and elasticity in the skin, and protecting against harmful external factors, including UV radiation [188,197,198,200].”

What the sources say

• Not checked yetcites [188] Michalak, 2017, Sources of vegetable dyes and their use in cosmetology, Pol. J. Cosmetol.
• Not checked yetcites [197] Nichols, 2010, Skin photoprotection by natural polyphenols: Anti-inflammatory, antioxidant and DNA repair mechanisms, Arch. Dermatol. Res. source
• Not checked yetcites [198] Zillich, 2015, Polyphenols as active ingredients for cosmetic products, Int. J. Cosmet. Sci. source
• Not checked yetcites [200] Chen, 2012, The role of antioxidants in photoprotection: A critical review, J. Am. Acad. Dermatol. source

In the paper

“In a randomized double-blind trial in 42 healthy patients taking 4 g/day of EPA or monounsaturated oleic acid for three months, an increase in the UV-induced erythematous threshold was observed, as was a decrease in the expression of the protein p53, a marker of DNA damage induced by UV radiation.”

What the sources say

• Not checked yetcites [187] Rhodes, 2003, Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers, Carcinogenesis source

In the paper

“Pomegranate fruit extract has been shown to reduce UVB-induced oxidative stress and the oxidation of skin proteins [209]”

What the sources say

• Not checked yetcites [209] Khan, 2012, Pomegranate fruit extract inhibits UVB-induced inflammation and proliferation by modulating NF-κB and MAPK signaling pathways in mouse skin, Photochem. Photobiol. source

In the paper

“Oils rich in EFAs improve skin hydration, have a regenerative effect on the damaged epidermal lipid barrier, and regulate skin metabolism.”

What the sources say

• Not checked yetcites [152] Michalak, 2018, Plant oils in cosmetology and dermatology, Pol. J. Cosmetol.
• Not checked yetcites [157] Burris, 2013, Acne: The role of medical nutrition therapy, J. Acad. Nutr. Diet. source

In the paper

“The results indicate that EPAs have a UV-filtering effect and suggest that longer-term supplementation may reduce the risk of skin cancer in humans [187].”

What the sources say

• Not checked yetcites [187] Rhodes, 2003, Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers, Carcinogenesis source

In the paper

“Polyphenols can also chelate transition metal cations (e.g., Cu2+ and Fe2+), thus preventing Haber–Weiss and Fenton reactions (which lead to the generation of the extremely reactive hydroxyl radical •OH) and also inhibiting the activity of many enzymes involved in free radical generation (e.g., xanthine oxidase, protein kinase and lipoxygenase).”

What the sources say

• Not checked yetcites [194] Miller, 1996, Structure-antioxidant activity relationships of flavonoids and phenolic acids, Free Radic. Biol. Med. source
• Not checked yetcites [195] Bravo, 1998, Polyphenols: Chemistry, dietary sources, metabolism, and nutritional significance, Nutr. Rev. source
• Not checked yetcites [202] Gupta, 2010, Recent updates on free radicals scavenging flavonoids: An overview, Asian. J. Plant Sci. source

In the paper

“Plant polyphenols are considered important substances for skin function, with hydrating, smoothing, softening, soothing and astringent effects [25,190,193,197,198,199].”

What the sources say

• Not checked yetcites [25] Anunciato, 2012, Carotenoids and polyphenols in nutricosmetics, nutraceuticals, and cosmeceuticals, J. Cosmet. Dermatol. source
• Not checked yetcites [190] Han, 2007, Dietary polyphenols and their biological significance, Int. J. Mol. Sci. source
• Not checked yetcites [193] Jain, 2010, Flavonoids as nutraceuticals. A review, Herba Pol.
• Not checked yetcites [197] Nichols, 2010, Skin photoprotection by natural polyphenols: Anti-inflammatory, antioxidant and DNA repair mechanisms, Arch. Dermatol. Res. source
• Not checked yetcites [198] Zillich, 2015, Polyphenols as active ingredients for cosmetic products, Int. J. Cosmet. Sci. source
• Not checked yetcites [199] Chuarienthong, 2010, Clinical efficacy comparison of anti-wrinkle cosmetics containing herbal flavonoids, Int. J. Cosmet. Sci. source