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Cited by 42Skin Protection and AgingPhytochemicals and Antioxidant ActivitiesGenomics, phytochemicals, and oxidative stress

Equol’s Anti-Aging Effects Protect against Environmental Assaults by Increasing Skin Antioxidant Defense and ECM Proteins While Decreasing Oxidative Stress and Inflammation

Open access
Lephart, Edwin·2018·Cosmetics
DOI 10.3390/cosmetics5010016
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Abstract

Environmental pollutants represent a major problem worldwide that cannot be passively avoided. It is known that skin sensitivities can result from environmental assaults, such as toxins and pollutants in air and water. Additionally, dermal assaults from wind and exposure to seasonal cold temperatures are known. All of these environmental assaults are associated with oxidative stress and the intracellular generation of reactive oxygen species (ROS), which damage DNA, lipids, proteins and mitochondrial function. Additionally, the influence of diet on dermal health and, especially, antioxidant defense in skin function are well established. In this regard, environmental pollution worldwide has generated a high demand for anti-pollution personal care products to protect the skin against the daily exposure of airborne toxins and various other assaults. Major cosmetic companies have anti-pollution personal care products but, in general, the products are formulated with commonly used active ingredients that have been retooled with market strategies to address current environmental pollution treatments. Equol is a new botanical active ingredient compound for skin applications. It has a polyphenolic chemical structure found in plant and food products, and is also classified as an isoflavonoid. Moreover, equol appears to address the need for an active ingredient in personal care products to protect against pollution assaults by increasing antioxidant defense, while inhibiting oxidative stress and inflammation. Separate sections covering equol’s enhanced (a) delivery mechanism into human skin; (b) antioxidant effects via Nrf2 activation; (c) effects on extracellular matrix proteins like collagen and elastin and; (d) protection against oxidative stress and inflammation are presented.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review argues that equol, a polyphenolic isoflavonoid, protects skin against environmental assaults (UV, pollution, cold, wind) by boosting antioxidant defense via Nrf2, increasing extracellular matrix proteins, and suppressing oxidative stress and inflammation. It synthesizes prior in vitro, ex vivo, and in vivo work rather than presenting new primary data.

Key findings

  • Topically applied equol increased gene and protein expression of collagen and elastin by approximately 2-fold and TIMP-1 by 5.4-fold, while significantly inhibiting elastase and MMP-1, MMP-3, and MMP-9 in long-term organotypic cell cultures.
  • Equol shows a unique epidermal "reservoir" delivery profile in Franz cell testing with tritiated equol, with a primary absorption peak at approximately 8 h and a secondary peak at around 28 h — a sustained release not seen with resveratrol, genistein, or 17β-estradiol.
  • Equol stimulates antioxidant enzymes (SOD2, TXNRD1), metallothioneins, and Nrf2 expression, and inhibits inflammatory mediators including IL-1, IL-6, IL-8, COX-1, and TNF receptor levels in human skin gene array studies.
  • Isomer potency differed: only 3 genes showed greatest significant expression with S-equol, whereas 16 genes did with R-equol and/or racemic equol; collagen type I expression in fibroblasts was greater with racemic versus S-equol at 1 and 10 nM. S-equol binds ERβ with a Ki of 0.7 nM versus 0.15 nM Kd for 17β-estradiol.

Methods

  • Narrative review covering sensitive skin perceptions, environmental sources of ROS (UVR, cold, air/water pollution, diet), equol's chemistry, and its dermal mechanisms.
  • Evidence cited is secondary: in vitro (human dermal fibroblast and organotypic cultures), ex vivo (Franz cell testing, human skin gene microarray), and in vivo (human repeat insult patch test; cosmetic use by more than 100,000 women).
  • No systematic search strategy, inclusion criteria, or meta-analysis is described.

Limitations

  • The author states he is an inventor on equol patents (U.S. and worldwide) for various health applications, though he declares no corporate/business, funding, or founder-sponsor conflict regarding the data presented.
  • The paper is a narrative review without primary data, systematic search methods, or quantitative synthesis; several key claims (e.g., the 2-fold collagen/elastin increase, 5.4-fold TIMP-1) are reported from cited prior studies rather than independently verified here.
  • The text notes that water pollution "has not been examined in reference to skin health," and that less research has been performed on environmental pollutants and skin aging than on UV — evident gaps in the evidence base the review relies on.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/cosmetics5010016

Cites

107 of 107 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 233 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Skin has a greater antioxidant defense capacity compared to internal organs due to protective structural and biological functioning of dermal layers.

    “Finally, and most importantly, the antioxidant defense capacity of the skin is greater compared to internal organs due to the protective structural and biological functioning of the dermal layers [1,2].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Farage, 2008, Intrinsic and extrinsic factors in skin ageing: A review, Int. J. Cosmet. Sci. source

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    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

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  • Premisecitation

    Environmental assaults (including pollutants, wind, cold, UV) are associated with oxidative stress and intracellular generation of ROS, which damage DNA, lipids, proteins, and mitochondrial function.

    “All of these environmental assaults are associated with oxidative stress and the intracellular generation of reactive oxygen species (ROS), which damage DNA, lipids, proteins and mitochondrial function.”
    • Also stated in: § 2. Perceptions of Sensitive Skin with Environmental Causes · plain
      “Exposure to sunlight, chemicals, pesticides, heavy metals, or other contaminants, plus various diseases, disorders, or trauma, along with unhealthy lifestyles, like tobacco smoking, alcohol consumption, and poor choice of diet, influence the generation of reactive oxygen species (ROS) [9].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

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    • cites [9] 2014, Environmental pollutants and lifestyle factors induce oxidative stress and poor prenatal development, Reprod. Biomed. Online source

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  • Premisecitation

    Oxidative stress is a major source of skin aging.

    “Additionally, it is well known that oxidative stress is a major source of skin aging, and the mechanisms by which it occurs have been reviewed [2,13,14].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

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    • cites [13] Kammeyer, 2015, Oxidative events and skin aging, Ageing Res. Rev. source

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    • cites [14] Natarajan, 2014, Multifaceted pathways protect human skin from UV radiation, Nat. Chem. Biol. source

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  • Premisecitation

    Free radicals and organic nanoparticles reduced human keratinocyte viability by apoptosis.

    “free radicals and organic nanoparticles reduced human keratinocyte viability by apoptosis [43,45,46]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [43] Schikowski, 2010, Airborne particle exposure and extrinsic skin aging, J. Investig. Dermatol. source

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    • cites [45] Dahmane, 2012, Free radicals and extrinsic aging, Dermatol. Res. Pract.

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    • cites [46] Pedala, 2012, Interaction between combustion-generated organic nanoparticles and biological systems: In vitro study of cell toxicity and apoptosis in human keratinocytes, Nanotoxicology source

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  • Premisecitation

    Air pollution exposure was significantly correlated with extrinsic skin aging, particularly pigment spots on the face and hands and, to a lesser extent, wrinkles.

    “Both reports suggested that air pollution exposure was significantly correlated with extrinsic skin aging, particularly to pigment spots on the face and hands and, to a lesser extent, for wrinkles [42,43].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [42] Lanuti, 2010, Effects of pollution on skin aging, J. Investig. Dermatol. source

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    • cites [43] Schikowski, 2010, Airborne particle exposure and extrinsic skin aging, J. Investig. Dermatol. source

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  • Classified as probably not a substantial claim. 34
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  • The quote only partly states this claim. 1

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    Premisecitation

    Skin aging can be classified by intrinsic (chronological) and extrinsic (photoaging) mechanisms.

    “Skin aging can be classified by intrinsic (chronological) and extrinsic (photoaging) mechanisms [1,2].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Farage, 2008, Intrinsic and extrinsic factors in skin ageing: A review, Int. J. Cosmet. Sci. source

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    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

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  • May combine two claims.

    Interpretationcitation

    Equol appears to potentially protect against pollution assaults via a variety of mechanisms to increase antioxidant defense, while also decreasing oxidative stress and inflammation.

    “Equol, a novel botanical active ingredient compound appears to potentially protect against pollution assaults via a variety of mechanisms to increase antioxidant defense, while also decreasing oxidative stress and inflammation [2].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

      Not checked in the free run.

    • Rests on an assumption: There is a need to identify and develop new active ingredients for skin applications that would address environmental assaults.
    • Rests on an assumption: Equol is a new botanical active ingredient compound for skin applications.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Diet can influence dermal health.

    “In reference to antioxidants defense, it is well known that diet can influence dermal health [3].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Katta, 2014, Diet and dermatology, the role of dietary intervention in skin disease, J. Clin. Aesthet. Dermatol.

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    Premisecitation

    Women in every region of the United States, like women in other parts of the world, reported some degree of skin sensitivity at fairly high levels (Farage et al., 2013).

    “A subsequent study by Farage et al. in 2013 confirmed several previous studies by demonstrating that women in every region of the United States, like women in other parts of the world, reported some degree of skin sensitivity at fairly high levels [5].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Farage, 2013, Sensitive skin in the United States: Survey of regional differences, Family Med. Med. Sci. Res.

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    Premisecitation

    Approximately 50 to almost 70% of women reported skin sensitivity worldwide (Farage, ~2008).

    “For example, approximately ten years ago, Farage from Procter and Gamble reported that 50 to almost 70% of women reported skin sensitivity worldwide [4].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Farage, 2008, Perceptions of sensitive skin: Changes in perceived severity and associations with environmental causes, Contact Dermat. source

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    Premisecitation

    Stress was the factor most strongly associated with perceived sensitive skin, especially on the face.

    “Moreover, the study by Farage in 2008 showed that stress was the factor most strongly associated with perceived sensitive skin especially on the face [4].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Farage, 2008, Perceptions of sensitive skin: Changes in perceived severity and associations with environmental causes, Contact Dermat. source

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  • May combine two claims.

    Premisecitation

    Exposure to sunlight, chemicals, pesticides, heavy metals, or other contaminants, plus various diseases, disorders, or trauma, along with unhealthy lifestyles (tobacco smoking, alcohol consumption, poor diet), influence the generation of ROS.

    “In regards to environmental factors exposure to sunlight, chemicals, pesticides, heavy metals, or other contaminants, plus various diseases, disorders, or trauma, along with unhealthy lifestyles, like tobacco smoking, alcohol consumption, and poor choice of diet, influence the generation of reactive oxygen species (ROS) [9].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] 2014, Environmental pollutants and lifestyle factors induce oxidative stress and poor prenatal development, Reprod. Biomed. Online source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Environmental factors are strongly associated with sensitive skin.

    “Environmental factors are strongly associated with sensitive skin [4].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Farage, 2008, Perceptions of sensitive skin: Changes in perceived severity and associations with environmental causes, Contact Dermat. source

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    Premisecitation

    Pollution is associated with generation of ROS, which damage DNA, lipids, proteins, mitochondrial function, and increases inflammation.

    “Pollution is associated with the generation of reactive oxygen species (ROS), which damage DNA, lipids, proteins, mitochondrial function, and increases inflammation [2].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

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  • Classified as probably not a substantial claim.

    Premisecitation

    If generation of ROS overwhelms endogenous antioxidant protection within the body, this leads to oxidative stress or damage.

    “If the generation of ROS overwhelms endogenous antioxidant protection within the body, this subsequently leads to oxidative stress or damage [9].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] 2014, Environmental pollutants and lifestyle factors induce oxidative stress and poor prenatal development, Reprod. Biomed. Online source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Vitamins A, C, and E from diet can act as antioxidants and are found in high concentrations in the epidermis and dermis.

    “Other molecules derived from our diet, such as vitamins A, C, and E, can also act as antioxidants which are found in high concentrations in the epidermis and dermis [2,[15][16][17].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

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    • cites [15] Shindo, 1994, Enzymic and non-enzymic antioxidants in epidermis and dermis in human skin, J. Investig. Dermayol. source

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    • cites [16] El-Missiry, M.A. (2012). Antioxidant Enzymes and Human Health, Chapter 1, Antioxidant Enzyme-InTech Science, Technology & Medicine. source

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    • cites [17] Pullar, J.M., Carr, A.C., and Vissers, M.C.M. (2107). The role of vitamin C in skin health. Nutrients, 9. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Sensitive skin is a common disorder that can induce changes in quality of life and has psychological consequences.

    “In general, sensitive skin is a common disorder that can induce changes in the quality of life and has psychological consequences [6].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Misery, 2017, Neuropsychiatric factors in sensitive skin, Clin. Dermatol. source

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    Premisecitation

    Psychosocial influences, as well as biological and environmental factors, contribute to skin sensitivity.

    “In this latter report, the authors concluded that it is increasingly recognized that psychosocial influences, as well as biological and environmental factors, contribute to skin sensitivity [5].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Farage, 2013, Sensitive skin in the United States: Survey of regional differences, Family Med. Med. Sci. Res.

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    Premisecitation

    In cold, windy outdoor conditions (-14 to 1 °C), human subjects exposed to low temperatures and high wind requested to go indoors at around 4-5 min, whereas low temperatures and low wind condition requests occurred around 8-10 min.

    “The human subjects exposed to low temperatures and high wind conditions displayed the quickest request interval to go indoors at around 4-5 min, whereas, low temperatures and low wind condition subject's requests to go indoors occurred around 8-10 min.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Briggs, 2017, Measuring facial cooling in outdoor windy winter conditions: An exploratory study, Int. J. Biometeorol. source

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    Premisecitation

    Extrinsic aging comes from external sources that increase oxidative stress, including sunlight (especially UVR), cold weather, and air/water pollution.

    “Extrinsic aging comes from external sources that increase oxidative stress, which include sunlight, especially ultraviolet radiation (UVR), temperature conditions, like cold weather, and air/water pollution.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

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    • cites [22] Valacchi, 2012, Cutaneous responses to environmental stressors, Ann. N. Y. Acad. Sci. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Cold weather was perceived by the highest percentage of subjects overall (81%) as causing skin irritation.

    “Notably, the investigation by Farage, in 2008, reported that of all the environmental factors, cold weather was perceived by the highest percentage of subjects overall (81%) as causing skin irritation [4].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Farage, 2008, Perceptions of sensitive skin: Changes in perceived severity and associations with environmental causes, Contact Dermat. source

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    Premisecitation

    Windy, cold conditions represent an environmental factor where facial cooling usually occurs within minutes, contributing to skin sensitivity.

    “Thus, windy, cold conditions represent an environmental factor, where facial cooling usually occurs within minutes, contributing to skin sensitivity [22,28].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22] Valacchi, 2012, Cutaneous responses to environmental stressors, Ann. N. Y. Acad. Sci. source

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    • cites [28] Briggs, 2017, Measuring facial cooling in outdoor windy winter conditions: An exploratory study, Int. J. Biometeorol. source

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    Premisecitation

    Most UV-induced oxidative stress is generated by UVA, which is more cytotoxic to human skin compared to UVB; UVB are mostly mutagenic; both stimulate generation of ROS.

    “Thus, most UV-induced oxidative stress is generated by UVA, which is more cytotoxic to human skin compared to UVB; whereas UVB are mostly mutagenic, both are known to stimulate the generation of ROS, [2,13,14,25]”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

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    • cites [13] Kammeyer, 2015, Oxidative events and skin aging, Ageing Res. Rev. source

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    • cites [14] Natarajan, 2014, Multifaceted pathways protect human skin from UV radiation, Nat. Chem. Biol. source

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    • cites [25] Swalwell, 2010, How mitochondria record the effects of UV exposure and oxidative stress using human skin as a model tissue, Mutagenesis source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Dietary intake of food sources containing antioxidants decreases ROS.

    “In this regard, the dietary intake of food sources containing antioxidants are known to decrease ROS [2,7,9,22].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

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    • cites [7] Anderson, R.R. (2012, January 6–7). Cosmegizmoceuticals: The Physics and Chemistry of Looking Better. Proceedings of the Society of Cosmetic Chemists Annual Meeting, New York, NY, USA.

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    • cites [9] 2014, Environmental pollutants and lifestyle factors induce oxidative stress and poor prenatal development, Reprod. Biomed. Online source

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    • cites [22] Valacchi, 2012, Cutaneous responses to environmental stressors, Ann. N. Y. Acad. Sci. source

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  • May combine two claims.

    Premisecitation

    UVA penetrates deeper into dermis to degrade collagen and elastin fibers via oxidative stress mechanisms that activate MMPs and damage mitochondrial structure/function, leading to extrinsic skin photoaging.

    “UVA (320-400 nm) at a higher wavelength range represents 95-98% of the total UV radiation reaching the Earth's surface can damage the epidermis and penetrates deeper into the dermis to degrade collagen and elastin fibers via oxidative stress mechanisms that in turn activate matrix metalloproteinases (MMPs) and damage mitochondrial structure/function that leads to extrinsic skin photoaging [2,13,14”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

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    • cites [13] Kammeyer, 2015, Oxidative events and skin aging, Ageing Res. Rev. source

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    • cites [14] Natarajan, 2014, Multifaceted pathways protect human skin from UV radiation, Nat. Chem. Biol. source

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    Premisecitation

    Intrinsic aging includes ROS production via normal oxidative metabolism within cells that is inevitable, but contributes modestly to skin aging compared to extrinsic aging.

    “For example, in intrinsic aging, there is ROS production via normal oxidative metabolism within cells that is inevitable, but contributes in a modest way to skin aging compared to extrinsic aging [2,18,19].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

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    • cites [18] Anderson, 2014, A role for human mitochondrial complex II in the production of reactive oxygen species in human skin, Redox Biol. source

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    • cites [19] Meadows, 2014, Age-related NADH oxidase (arNOX)-catalyzed oxidative damage to skin protein, Arch. Dermatol. Res. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    UVR contributes approximately 5%, visible light about 42%, and infrared light around 53% of the content of sunlight.

    “There are different types of solar radiation: UVR contributes approximately 5%, visible light about 42%, and infrared light around 53% of the content of sunlight [13,23].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [13] Kammeyer, 2015, Oxidative events and skin aging, Ageing Res. Rev. source

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    • cites [23] Freedberg, I.M., Eisen, A.Z., Wolff, K.F., Austen, L.A., Goldsmith, L.A., and Katz, S.I. (2003). Acute and chronic effects of ultraviolet radiation on the skin. Fitzpatrick’s Dermatology in General Medicine, McGraw-Hill. [6th ed.].

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    Premisecitation

    Up to 80-90% of skin aging is due to deleterious effects of sunlight or photoaging.

    “It is thought that up to 80-90% of skin aging is due to the deleterious effects of sunlight or photoaging [2,13].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

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    • cites [13] Kammeyer, 2015, Oxidative events and skin aging, Ageing Res. Rev. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Cold environments or lengthy exposures can cause dry skin conditions or aggravate common dermatoses, such as atopic dermatitis and psoriasis.

    “These are especially true for those who work in cold environments or where being outside in cold temperatures with lengthy exposures can cause dry skin conditions or aggravate common dermatoses, such as atopic dermatitis and psoriasis [27].”
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    • cites [27] Makinen, 2009, Health problems in cold work, Ind. Health source

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    Premisecitation

    UVB penetrates into epidermal cells, can damage DNA and activate a cascade leading to generation of ROS and increased photo-aging.

    “UVB (280-320 nm), while representing only 2-5% of the sun's emissions, penetrates into epidermal cells, can damage DNA and activate a cascade of events leading to the generation of ROS and increased photo-aging [2,13,23,24].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

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    • cites [13] Kammeyer, 2015, Oxidative events and skin aging, Ageing Res. Rev. source

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    • cites [23] Freedberg, I.M., Eisen, A.Z., Wolff, K.F., Austen, L.A., Goldsmith, L.A., and Katz, S.I. (2003). Acute and chronic effects of ultraviolet radiation on the skin. Fitzpatrick’s Dermatology in General Medicine, McGraw-Hill. [6th ed.].

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    • cites [24] Wlaschek, 2001, Solar UV irradiation and dermal photoaging, J. Photochem. Photobiol. B source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    UVA and UVB rays make up 95-98% and 2-5%, respectively, of the UV radiation reaching human skin.

    “UVA and UVB rays make up 95-98% and 2-5%, respectively, of the UV radiation reaching human skin [23].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Freedberg, I.M., Eisen, A.Z., Wolff, K.F., Austen, L.A., Goldsmith, L.A., and Katz, S.I. (2003). Acute and chronic effects of ultraviolet radiation on the skin. Fitzpatrick’s Dermatology in General Medicine, McGraw-Hill. [6th ed.].

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    Premisecitation

    S-equol binds ERβ approximately 1/5 as well as 17β-estradiol, while having low affinity for ERα.

    “Remarkably, S-equol binds ERβ approximately 1/5, as well as 17β-estradiol, while having low affinity for ERα [2,78,80].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

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    • cites [78] Lephart, E.D. (2017). Resveratrol, 4′ Acetoxy Resveratrol, R-Equol, Racemic Equol or S-Equol as Cosmeceuticals to Improve Dermal Health. Int. J. Mol. Sci., 18. source

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    • cites [80] Setchell, 2005, S-equol, a potent ligand for estrogen receptor β, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora, Am. J. Clin. Nutr. source

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    Premisecitation

    Dietary (via vitamins) and supplementation of antioxidant-rich ingredients (e.g., polyphenolic compounds like green tea or beta-carotene, lycopene) improve parameters of skin structure, density and elasticity and protect against damaging influence of UV exposure.

    “Moreover, both dietary (via vitamins) and supplementation of antioxidant-rich ingredients (i.e., polyphenolic compounds like green tea or beta-carotene, lycopene, etc.) have been reported to improve parameters of skin structure, density and elasticity and protect against the damaging influence of UV exposure [64,67].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [64] Draelos, 2013, Aging Skin: The role of diet: Facts and controversies, Clin. Dermatol. source

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    • cites [67] Heinrich, 2017, Anti-aging by nutricosmetics, Aktuelle Dermatol. source

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  • May combine two claims.

    Premisereasoning

    S-equol is classified as a selective estrogen receptor modulator (SERM) with high affinity for ERβ.

    “Thus, S-equol is classified as a selective estrogen receptor modulator (SERM) with high affinity for ERβ.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

      Not checked in the free run.

    • cites [78] Lephart, E.D. (2017). Resveratrol, 4′ Acetoxy Resveratrol, R-Equol, Racemic Equol or S-Equol as Cosmeceuticals to Improve Dermal Health. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

    • cites [80] Setchell, 2005, S-equol, a potent ligand for estrogen receptor β, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora, Am. J. Clin. Nutr. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Equol (presumably S-equol) is present naturally in some plants, such as beans, cabbage, and lettuces, having a botanical origin.

    “Thus, equol (presumably S-equol) is present naturally in some plants, such as beans, cabbage, and lettuces, having a botanical origin [2,78,79]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

      Not checked in the free run.

    • cites [78] Lephart, E.D. (2017). Resveratrol, 4′ Acetoxy Resveratrol, R-Equol, Racemic Equol or S-Equol as Cosmeceuticals to Improve Dermal Health. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

    • cites [79] Setchell, 2010, Equol: History, chemistry, and formation, J. Nutr. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ambient air pollution negatively impacts skin health via four general mechanisms: generation of ROS; induction of inflammatory cascade and impairment of skin barrier; activation of AHR stimulating skin aging genes such as MMPs that degrade collagen; and alterations to skin microflora.

    “two recent reviews have summarized the recognized negative impact of ambient air pollution on skin health, which suggested four general mechanisms by which this occurs: (1) generation of ROS; (2) induction of the inflammatory cascade and subsequent impairment of the skin barrier; (3) activation of the AHR which stimulates the expression skin aging genes such as MMPs that degrade collagen; and (4)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [60] Mancebo, 2015, Recognizing the impact of ambient air pollution on skin health, J. Eur. Acad. Dermatol. Venereol. source

      Not checked in the free run.

    • cites [61] Koohgoli, 2017, Bad air gets under your skin, Exp. Dermatol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Skin disorders can result from poor nutrition, such as scurvy (vitamin C deficiency) and atopic dermatitis associated with essential fatty acid deficiency.

    “Dermatologist are well aware that skin disorders can result from poor nutrition, such as scurvy (vitamin C deficiency), atopic dermatitis, which is associated with essential fatty acid deficiency, and people who do not eat well do not look well; meaning eating better results in”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [3] Katta, 2014, Diet and dermatology, the role of dietary intervention in skin disease, J. Clin. Aesthet. Dermatol.

      Not checked in the free run.

    • cites [17] Pullar, J.M., Carr, A.C., and Vissers, M.C.M. (2107). The role of vitamin C in skin health. Nutrients, 9. source

      Not checked in the free run.

    • cites [64] Draelos, 2013, Aging Skin: The role of diet: Facts and controversies, Clin. Dermatol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Indoor air pollution from cooking accelerated skin aging in Chinese women, and atopic dermatitis increased from other indoor pollutants, such as PVCs from wallpaper.

    “indoor air pollution from cooking accelerated skin aging in Chinese women, and atopic dermatitis increased from other indoor pollutants, such as polyvinyl chloride (PVCs) from wallpaper [51,52]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [51] Li, 2015, Epidemiological evidence that indoor air pollution from cooking with solid fuels accelerates skin aging in Chinese women, J. Dermatol. Sci. source

      Not checked in the free run.

    • cites [52] Kim, Y.-K., Kim, H., Lim, D.-H., Lee, Y.-K., and Kim, J.H. (2016). Effects of indoor air pollutants on atopic dermatitis. Int. J. Environ. Res. Public Health, 13. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Dietary sources commonly known for antioxidant properties include vitamin A, C, and E along with carotenoids, lipoic acid, and phenolic compounds found in plant products like fruits and vegetables.

    “Dietary sources that are commonly known for their antioxidant properties include vitamin A, C, and E along with other antioxidants in carotenoids, lipoic acid, and phenolic compounds found in abundance in many plant products like fruits and vegetables [2,17,66].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

      Not checked in the free run.

    • cites [17] Pullar, J.M., Carr, A.C., and Vissers, M.C.M. (2107). The role of vitamin C in skin health. Nutrients, 9. source

      Not checked in the free run.

    • cites [66] Lee, 2004, Reactive oxygen species, aging and antioxidative nutraceuticals, Compr. Rev. Food Sci. Food Saf. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Consumption of the Mediterranean diet increased longevity and reduced age-related diseases, lowered levels of oxidative stress, and prevented cellular senescence in human epithelial cells.

    “For example, studies have shown that consumption of the Mediterranean diet increased longevity and reduced age-related diseases, lowered levels of oxidative stress, and prevented cellular senescence in human epithelial cells [31].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Naidoo, K., and Birch-Machin, M.A. (2017). Oxidative stress and ageing: The influence of environmental pollution, sunlight and diet on skin. Cosmetics, 4. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Equol is classified as a polyphenolic compound.

    “Traditionally, equol is classified as a polyphenolic compound.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

      Not checked in the free run.

    • cites [77] Park, 2015, The pharmacology of resveratrol in animals and humans, Biochim. Biophys. Acta source

      Not checked in the free run.

    • cites [78] Lephart, E.D. (2017). Resveratrol, 4′ Acetoxy Resveratrol, R-Equol, Racemic Equol or S-Equol as Cosmeceuticals to Improve Dermal Health. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Vitamin C mixtures prevented ozone-induced oxidative damage in human keratinocytes.

    “In this regard, a recent study by Valacchi in 2015 showed that vitamin C mixtures prevented ozone-induced oxidative damage in human keratinoctyes [68].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Valacchi, G., Sticozzi, C., Belmonte, G., Cervellati, F., Demaude, J., Chen, N., Krol, Y., and Oresajo, C. (2015). Vitamin C compound mixtures prevent ozone-induced oxidative damage in human keratinocytes as initial assessment of pollution protection. PLoS ONE, 10. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Decreased skin barrier function and increased facial hyperpigmentation (lentigines) from ambient PMs are known to increase inflammatory skin diseases, ROS and MMPs that degrade collagen.

    “decreased skin barrier function and increased facial hyperpigmentation (lentigines) from ambient PMs that are known to increase inflammatory skin diseases, ROS and matrix metalloproteinases (MMPs) that degrade collagen [53][54][55][56][57]”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [53] Pan, 2015, The impact of urban particulate pollution on skin barrier function and the subsequent drug absorption, J. Dermatol. Sci. source

      Not checked in the free run.

    • cites [54] Roberts, 2015, Pollution as a risk factor for the development of melasma and other skin disorders of facial hyperpigmentation-is there a case to be made?, J. Drugs Dermatol.

      Not checked in the free run.

    • cites [55] Kim, 2016, Air pollution and skin diseases: Adverse effects of airborne particulate matter on various skin diseases, Life Sci. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Many dietary antioxidants are incorporated into the epidermal and dermal layers of human skin.

    “Many of these dietary antioxidants are incorporated into the epidermal and dermal layers of human skin [15,17].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [15] Shindo, 1994, Enzymic and non-enzymic antioxidants in epidermis and dermis in human skin, J. Investig. Dermayol. source

      Not checked in the free run.

    • cites [17] Pullar, J.M., Carr, A.C., and Vissers, M.C.M. (2107). The role of vitamin C in skin health. Nutrients, 9. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Both equol and resveratrol are strong antioxidants when topically applied.

    “Notably, both equol and resveratrol are known to be strong antioxidants when topically applied”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Nrf2 is a master regulator of the transcriptional response to oxidative stress, structurally and functionally conserved from insects to humans.

    “Finally, nuclear-factor-erythroid 2-related factor 2 (Nrf2) is a master regulator of the transcriptional response to oxidative stress, and it is structurally and functionally conserved from insects to humans [69].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [69] Lacher, 2015, Beyond antioxidant genes in the ancient Nrf2 regulatory network, Free Radic. Biol. Med. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A recent review by Greenwald et al., 2016, described a need for a Nrf2 activator in human skin to maintain dermal redox balance in modulating the Keap1-Nrf2 pathway for antioxidant defense.

    “Finally, a recent review by Greenwald et al., in 2016, described a need for a Nfr2 activator in human skin to maintain dermal redox balance in modulating the Keap 1-Nrf2 pathway for antioxidant defense [76].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [76] Greenwald, M.B.-Y., Ben-Sasson, S., Blanco-Peled, H., and Kohen, R. (2016). Skin redox balance maintenance: The need for a Nrf2-activator delivery system. Cosmetics, 3. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    R-equol has weak affinity for either ER and weak estrogenic properties at best.

    “Conversely, R-equol has weak affinity for either ER and, in general, has weak estrogenic properties, at best [2,78].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

      Not checked in the free run.

    • cites [78] Lephart, E.D. (2017). Resveratrol, 4′ Acetoxy Resveratrol, R-Equol, Racemic Equol or S-Equol as Cosmeceuticals to Improve Dermal Health. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    More than 100,000 women have used topically-applied equol with great success.

    “more than 100,000 women have used topically-applied equol with great success [2,78,84,85].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

      Not checked in the free run.

    • cites [78] Lephart, E.D. (2017). Resveratrol, 4′ Acetoxy Resveratrol, R-Equol, Racemic Equol or S-Equol as Cosmeceuticals to Improve Dermal Health. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

    • cites [84] Gopaul, 2012, Biochemical investigation and gene analysis of equol: A plant and soy-derived isoflavonoid with anti-aging and antioxidant properties with potential human skin applications, Biofactors source

      Not checked in the free run.

    • cites [85] Lephart, 2013, Protective effects of equol and their polyphenolic isomers against dermal aging: Microarray/protein evidence with clinical implications and unique delivery into human skin, Pharm. Biol. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Nrf2 activation increases antioxidant gene expression of several proteins.

    “since Nrf2 activation is known to increase antioxidants gene expression of several proteins”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [6] Misery, 2017, Neuropsychiatric factors in sensitive skin, Clin. Dermatol. source

      Not checked in the free run.

    • cites [97] Jackson, R.L., Greiwe, J.S., and Schwen, R.J. (2014). S-equol, an antioxidant metabolite of soy dadizein, and oxidative stress in aging: A focus on skin and the cardiovascular system. Aging: Oxidative Stress and Dietary Antioxidants, Elsevier Inc. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Antioxidants significantly increased epidermal thickness, elasticity, and stratum corneum moisture content.

    “antioxidants significantly increased epidermal thickness, elasticity, and stratum corneum moisture content [87].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [87] Lademann, 2016, Influence of topical, systematic and combined application of antioxidants on barrier properties of the human skin, Skin Pharm. Physiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Franz cell testing using tritiated equol penetration into human skin has shown percutaneous absorption and skin content distribution among the epidermal and dermal compartments.

    “Franz cell testing using tritiated equol penetration into human skin has shown: (1) the percutaneous absorption and; (2) skin content distribution among the epidermal and dermal compartments.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [85] Lephart, 2013, Protective effects of equol and their polyphenolic isomers against dermal aging: Microarray/protein evidence with clinical implications and unique delivery into human skin, Pharm. Biol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Haem oxygenase is a protector of lipid peroxidation and is part of the MAPK pathway that results in activation of antioxidant genes/enzyme via the Nrf2/KEAP1/ARE pathway.

    “It is known from cardiovascular studies examining dietary isoflavones that haem oxygenase is a protector of lipid peroxidation and is part of the mitogen-activated protein kinase (MAPK) pathway that results in the activation of antioxidant genes/enzyme via the Nrf2/KEAP 1/ARE pathway [95].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [95] Mann, 2009, Targeting the redox sensitive Nrf2-Keep1 defense pathway in cardiovascular disease: Protection afforded by dietary isoflavones, Curr. Opin. Pharmacol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Equol is the only cosmetic ingredient where in vitro gene expression biomarkers have been shown to correspond to protein expression levels, validating that gene activation results in a parallel change in gene product or protein levels.

    “equol is the only cosmetic ingredient, where in vitro gene expression biomarkers have been shown to correspond to protein expression levels validating that gene activation results in a parallel change in gene product or protein levels [86].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [86] Lephart, E.D. (2017). Human Skin Gene Expression Doesn’t Correlate with Protein Expression? Unless Both Parameters Are Quantified. J. Cosmet. Dermatol. source

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    Topically applied equol forms an epidermal reservoir that releases into the dermis with a primary absorption peak at approximately 8 h and a secondary peak at around 28 h.

    “forms an equol”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [85] Lephart, 2013, Protective effects of equol and their polyphenolic isomers against dermal aging: Microarray/protein evidence with clinical implications and unique delivery into human skin, Pharm. Biol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    S-equol is an intestinal metabolite in animals and humans when precursor compounds like daidzein are consumed, but most humans do not generate S-equol concentrations at high levels.

    “S-equol is an intestinal metabolite in animals and humans, when precursor compounds (like daidzein) are consumed but, in general, most humans do not generate S-equol concentrations at high levels [2,78,79].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

      Not checked in the free run.

    • cites [78] Lephart, E.D. (2017). Resveratrol, 4′ Acetoxy Resveratrol, R-Equol, Racemic Equol or S-Equol as Cosmeceuticals to Improve Dermal Health. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

    • cites [79] Setchell, 2010, Equol: History, chemistry, and formation, J. Nutr. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    S-equol is a metabolite of daidzein and is found in plant products such as beans, cabbage, lettuces, tofu, and other food and animal products like eggs and cow's milk.

    “S-equol, which is a metabolite of daidzein (an isoflavone found in plant and food products), has been found in plant products such as beans, cabbage, lettuces, tofu, and other food and animal products, like eggs and cow's milk, as reviewed elsewhere [2,78]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

      Not checked in the free run.

    • cites [78] Lephart, E.D. (2017). Resveratrol, 4′ Acetoxy Resveratrol, R-Equol, Racemic Equol or S-Equol as Cosmeceuticals to Improve Dermal Health. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    This sustained release of topically-applied equol acts upon fibroblasts and promotes continued positive effects on skin health and addresses oxidative stress.

    “This sustained release of topically-applied equol acts upon fibroblasts and promotes continued positive effects on skin health and addresses the issues of oxidative stress [2,85].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

      Not checked in the free run.

    • cites [85] Lephart, 2013, Protective effects of equol and their polyphenolic isomers against dermal aging: Microarray/protein evidence with clinical implications and unique delivery into human skin, Pharm. Biol. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Equol may increase Nrf2 levels and/or bind to estrogen-responsive elements (EREs) in the promoter region of the Nrf2 gene and/or increase gene expression of other antioxidant genes.

    “Specifically, equol may increase Nrf2 levels and/or bind to the estrogen-responsive elements (EREs) in the promoter region the Nrf2 gene and/or increase gene expression of other antioxidant genes [2,97].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

      Not checked in the free run.

    • cites [97] Jackson, R.L., Greiwe, J.S., and Schwen, R.J. (2014). S-equol, an antioxidant metabolite of soy dadizein, and oxidative stress in aging: A focus on skin and the cardiovascular system. Aging: Oxidative Stress and Dietary Antioxidants, Elsevier Inc. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationcitation

    Equol appears to be an exceptional choice for potential incorporation into human skin applications, especially for women, due to its multiple positive actions to improve dermal health.

    “it appears to be an exceptional choice for potential incorporation into human skin applications, especially for women, due to its multiple positive actions to improve dermal health [2,78,108].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

      Not checked in the free run.

    • cites [78] Lephart, E.D. (2017). Resveratrol, 4′ Acetoxy Resveratrol, R-Equol, Racemic Equol or S-Equol as Cosmeceuticals to Improve Dermal Health. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

    • cites [108] Lephart, E.D. (2018). A review of the role of estrogen in dermal aging and facial attractiveness in women. J. Cosmet. Dermatol., in press. source

      Not checked in the free run.

    • Rests on an assumption: Environmental pollutants speed up skin aging by breaking down extracellular matrix proteins like collagen and elastin.
    • Rests on an assumption: Environmental pollution worldwide has generated a high demand for anti-pollution personal care products to protect the skin against daily exposure to airborne toxins.
    • Rests on an assumption: Consumers are demanding anti-aging ingredients with enhanced antioxidant defense and protection against oxidative stress (ROS).

  • May combine two claims.

    Interpretationcitation

    Equol appears to address the need as a new active ingredient in personal care products to protect against pollution assaults by increasing antioxidant defense, while inhibiting oxidative stress and inflammation.

    “Moreover, equol appears to address the need as a new active ingredient in personal care products to protect against pollution assaults by increasing antioxidant defense, while inhibiting oxidative stress and inflammation [2,78].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

      Not checked in the free run.

    • cites [78] Lephart, E.D. (2017). Resveratrol, 4′ Acetoxy Resveratrol, R-Equol, Racemic Equol or S-Equol as Cosmeceuticals to Improve Dermal Health. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

    • Rests on an assumption: Environmental pollutants speed up skin aging by breaking down extracellular matrix proteins like collagen and elastin.
    • Rests on an assumption: Environmental pollution worldwide has generated a high demand for anti-pollution personal care products to protect the skin against daily exposure to airborne toxins.
    • Rests on an assumption: Consumers are demanding anti-aging ingredients with enhanced antioxidant defense and protection against oxidative stress (ROS).

  • May combine two claims.

    Premisecitation

    Only three genes displayed the greatest significant expression by S-equol, whereas 16 genes displayed the greatest significant levels by R-equol and/or racemic equol.

    “only three genes displayed the greatest significant expression by S-equol, whereas 16 genes displayed the greatest significant levels (either stimulation or inhibition) by R-equol and/or racemic equol”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [85] Lephart, 2013, Protective effects of equol and their polyphenolic isomers against dermal aging: Microarray/protein evidence with clinical implications and unique delivery into human skin, Pharm. Biol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Photoaging or extrinsic aging due to UV light and environmental pollutants trigger oxidative stress and formation of ROS that damages DNA, mitochondrial function, protein, lipids, and results in declination of antioxidant levels.

    “photoaging or extrinsic aging due to exposure to UV light along with assaults from environmental pollutants (such as particles, wind or cold) trigger oxidative stress and the formation of ROS that damages DNA, mitochondrial function, protein, lipids, and results in the declination of antioxidant levels [2,13,14].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

      Not checked in the free run.

    • cites [13] Kammeyer, 2015, Oxidative events and skin aging, Ageing Res. Rev. source

      Not checked in the free run.

    • cites [14] Natarajan, 2014, Multifaceted pathways protect human skin from UV radiation, Nat. Chem. Biol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    NF-KB is expressed in all cell types, is involved in the oxidative stress mechanism by expression of numerous genes such as cytokines, and plays a major role in the pathology of inflammatory disease.

    “NF-kappB (NF-KB) has been studied for more than 25 years and is known to be expressed in all cell types, where it is involved in the oxidative stress mechanism by the expression of numerous genes, such as the cytokines, and plays a major role in the pathology of inflammatory disease [104,105].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [104] Gupta, 2010, Inhibiting NFkappaB activation by small molecules as a therapeutic strategy, Biochim. Biophys. Acta source

      Not checked in the free run.

    • cites [105] Hayden, 2012, NF-kB, the first quarter-century: Remarkable progress and outstanding questions, Genes Dev. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Equol inhibits NF-KB in macrophages and blocks production of free radicals like nitric oxide (NO).

    “Equol has been shown to inhibit NF-KB in macrophages and block the production of free radicals like nitric oxide (NO) [106,107].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [106] Kang, 2005, Estrogen receptor-independent inhibition of tumor necrosis factor-alpha gene expression by phytoestrogen equol is mediated by blocking nuclear factor-kappa B activation in mouse macrophages, Biochem. Pharm. source

      Not checked in the free run.

    • cites [107] Kang, 2007, Equol inhibits nitric oxide production and inducible nitric oxide synthase gene expression through down-regulating the activation of Akt, Int. Immunopharmacol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Photoaging and environmental pollutants increase oxidative stress (ROS).

    “The major factors of extrinsic skin aging include: photoaging and environmental pollutants that, in turn, increase oxidative stress (ROS).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2] Lephart, 2016, Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev. source

      Not checked in the free run.

61 of 61

  • The paper relies on this without support.

    There is a need to identify and develop new active ingredients for skin applications that would address environmental assaults.

    “However, there is always a need to identify and develop new active ingredients for skin applications that would address environmental assaults.”

  • The paper relies on this without support.

    Equol is a new botanical active ingredient compound for skin applications.

    “Equol is a new botanical active ingredient compound for skin applications.”

  • The paper relies on this without support.

    Equol has a polyphenolic chemical structure found in plant and food products, and is classified as an isoflavonoid.

    “It has a polyphenolic chemical structure found in plant and food products, and is also classified as an isoflavonoid.”

  • The paper relies on this without support.

    Environmental pollution worldwide has generated a high demand for anti-pollution personal care products to protect the skin against daily exposure of airborne toxins and various other assaults.

    “In this regard, environmental pollution worldwide has generated a high demand for anti-pollution personal care products to protect the skin against the daily exposure of airborne toxins and various other assaults.”

  • The paper relies on this without support.

    Environmental pollutants speed up skin aging by breaking down extracellular matrix proteins like collagen and elastin.

    “Since environmental pollutants are known to speed up the aging process by breaking down the vital extracellular matrix proteins like collagen and elastin”

  • The paper relies on this without support.

    Environmental pollution worldwide has generated a high demand for anti-pollution personal care products to protect the skin against daily exposure to airborne toxins.

    “environmental pollution worldwide has generated a high demand for anti-pollution personal care products to protect the skin against the daily exposure of airborne toxins”

  • The paper relies on this without support.

    Consumers are demanding anti-aging ingredients with enhanced antioxidant defense and protection against oxidative stress (ROS).

    “Consumers are demanding anti-aging ingredients with enhanced antioxidant defense and protection against oxidative stress (ROS).”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Up to 80-90% of skin aging is due to environmental and xenobiotic agents (extrinsic aging).

    “However, it has been reported that up to 80–90% of skin aging is due to environmental and xenobiotic agents (extrinsic aging) [26, 28].”

    From Antioxidants from Plants Protect against Skin Photoaging (2018) · cites this paper as [28]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • UVB's share of sunlight is confused with its share of UV radiation

    Minor

    The text says UVB is 2-5% of all the sun's emissions, but elsewhere says UVB is 2-5% of UV radiation, which itself is approximately 5% of sunlight. Those are different shares of the total.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 3

  1. Anderson, R.R. (2012, January 6–7). Cosmegizmoceuticals: The Physics and Chemistry of Looking Better. Proceedings of the Society of Cosmetic Chemists Annual Meeting, New York, NY, USA.
  2. Vierkotter, 2011, Environmental pollution and skin aging, Hautarzt, 62, 577
  3. Nikolic, 2010, Air pollution and skin effects in children, J. Environ. Prot. Ecol., 11, 1215

Cited by

Sorted by citations

Related

Authors
Lephart, E.
Affiliations
Brigham Young University (US)
Corresponding author
Lephart, Edwin
ORCID
Lephart, Edwin
Venue
Cosmetics
Publisher
MDPI AG
Published
2018-01-29
Volume
5
Issue
1
Pages
16
ISSN
2079-9284 (ISSN-L)
DOI
10.3390/cosmetics5010016
OpenAlex
W2790404294
Semantic Scholar
f84b25df50ca40dd9bd516bb33f6ae6309938383
Cited by
42
References
107
Citations by year
2026: 2 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 10 · 2021: 6 · 2020: 3 · 2019: 4 · 2018: 4
FWCI
4.62
Type
journal article
Language
en
Open access
Licence
Locations
  • Cosmetics (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
BYU LS/TTO (19-2215)
Topics
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
  • Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Keywords
equol, isoflavonoids, anti-aging, oxidative stress, inflammation, reactive oxygen species, Nrf2 activation, extracellular matrix proteins, collagen, elastin, environmental pollution, personal care products, skin protection, polyphenols, topical delivery

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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