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Cited by 365Skin Protection and AgingPhytochemicals and Antioxidant Activitiesmelanin and skin pigmentation

Ferulic Acid Stabilizes a Solution of Vitamins C and E and Doubles its Photoprotection of Skin

Open access
Lin, Fu-Hsiung, Lin, Jing-Yi, Gupta, Ravindra D., Tournas, Joshua A., Burch, James A., Angelica Selim, M., Monteiro-Riviere, Nancy A., Grichnik, James M. +2 more·2005·Journal of Investigative Dermatology
DOI 10.1111/j.0022-202x.2005.23768.x
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Abstract

Ferulic acid is a potent ubiquitous plant antioxidant. Its incorporation into a topical solution of 15%l-ascorbic acid and 1%alpha-tocopherol improved chemical stability of the vitamins (C+E) and doubled photoprotection to solar-simulated irradiation of skin from 4-fold to approximately 8-fold as measured by both erythema and sunburn cell formation. Inhibition of apoptosis was associated with reduced induction of caspase-3 and caspase-7. This antioxidant formulation efficiently reduced thymine dimer formation. This combination of pure natural low molecular weight antioxidants provides meaningful synergistic protection against oxidative stress in skin and should be useful for protection against photoaging and skin cancer.

AI snapshot

Written from the paper’s full text.

TL;DR

Adding ferulic acid to a topical solution of vitamins C and E improved the vitamins’ chemical stability and raised photoprotection against simulated sunlight in pig skin from roughly fourfold to about eightfold. The authors propose that this triple antioxidant combination may help prevent photoaging and skin cancer.

Key findings

  • A formulation containing 0.5% ferulic acid, 15% L-ascorbic acid, and 1% α-tocopherol provided approximately 8-fold photoprotection, compared with about 4-fold for ferulic acid alone or vitamins C + E alone, as measured by erythema and sunburn cell counts.
  • After 1 month at 45°C, ferulic acid preserved more than 90% of L-ascorbic acid and 100% of α-tocopherol.
  • The triple combination reduced activation of caspase-3 and caspase-7 after 4× and 8× minimal erythema dose (MED) of solar-simulated radiation; at 8× MED, protection was nearly complete.
  • Thymine dimer formation after 8× MED was about one-third positive with ferulic acid alone, about 15% positive with vitamins C + E, and completely negative with the triple combination.

Methods

  • Weanling white Yorkshire pigs were pretreated topically for 4 consecutive days with vehicle, 0.5% ferulic acid, 15% L-ascorbic acid + 1% α-tocopherol, or the triple combination, then exposed to solar-simulated radiation from 2× to 10× MED at 2× MED intervals, with evaluation 24 hours later.
  • Outcomes included antioxidant protection factor, colorimetric erythema, sunburn cell counts, western blotting for caspase-3 and caspase-7, and immunohistochemistry for thymine dimers.
  • Results are reported as mean ± SD, with p-values from two-tailed Student’s t-tests; photoprotection experiments used n = 6, and caspase experiments used n = 3.

Limitations

  • The paper states that the mechanism by which ferulic acid stabilizes vitamins C and E is unknown, that no dose-response effect supported a sunscreen mechanism, and that the authors could not yet measure effects on UV-induced 8-oxo guanine formation.
  • Evident from the text: the main photoprotection experiments were performed in pig skin rather than human skin, and sample sizes were small (n = 6 or n = 3 depending on assay). The paper does not include a dedicated limitations section.

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

Integrity signals

Registry

Crossref · 10.1111/j.0022-202x.2005.23768.x

Cites

45 of 45 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

1 of 20 cited sources checked · 1 supported · 0 flagged

  • Premisecitation

    A recent study of three high SPF broad-screen sunscreens revealed that at 2 mg per cm2 application, UVA-induced free radical formation was reduced only 55% with even worse protection when application levels were decreased.

    “Indeed a recent study of three high SPF broad-screen sunscreens revealed that at 2 mg per cm 2 application, UVAinduced free radical formation was reduced only 55% with even worse protection when application levels were decreased (Haywood et al, 2003).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Haywood et al, 2003 source
  • Findingown data

    Antioxidant solutions protected against activation of caspase-3 by 4× and 8× MED of solar-simulated radiation.

    “Figure 2a reveals protection by antioxidant solutions of activation of caspase-3 by 4 Â and 8 Â MED of solar-simulated radiation.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The porcine skin model used in the experiments is predictive of human skin photoprotection.
    • Rests on an assumption: Activation of caspase-3 and caspase-7 is a valid marker of apoptosis in this model.
  • Findingown data

    Addition of 0.5% ferulic acid to the solution of 15% L-ascorbic acid and 1% α-tocopherol doubled photoprotection when applied topically to skin from 4-fold to approximately 8-fold.

    “Its incorporation into a topical solution of 15% L-ascorbic acid and 1% a-tocopherol improved chemical stability of the vitamins (C þ E) and doubled photoprotection to solarsimulated irradiation of skin from 4-fold to approximately 8-fold as measured by both erythema and sunburn cell formation.”
    • Also stated in: § Abstract · plain
      “We were surprised to find that in addition to improving stability, adding 0.5% ferulic acid to the solution of 15% L- ascorbic acid and 1% a-tocopherol doubled photoprotection when applied topically to skin from 4-to 8-fold.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The porcine skin model used in the experiments is predictive of human skin photoprotection.
  • Findingown data

    Our studies revealed no evidence of a dose-response effect to support a sunscreen mechanism.

    “Our studies revealed no evidence of a dose-response effect to support a sunscreen mechanism (Fig 5).”
    Quote in the paperSubstantial claim
  • Findingown data

    With 8× MED irradiation, protection of caspase-7 by vitamins C, E, and ferulic acid is virtually complete.

    “Figure 2d shows relative antioxidant protection, which is virtually complete by vitamins C, E and ferulic acid.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The porcine skin model used in the experiments is predictive of human skin photoprotection.
    • Rests on an assumption: Activation of caspase-3 and caspase-7 is a valid marker of apoptosis in this model.
  • May combine two claims. 16
  • The quote only partly states this claim. 2
  • Classified as probably not a substantial claim. 5

  • May combine two claims.

    Findingown data

    After 8× MED, ferulic acid-treated skin was about one third positive for thymine dimers, and vitamin C+E-treated skin was about 15% positive with less intense fluorescence.

    “After 8 Â MED, ferulic acidtreated skin was about one third positive (Fig 4b) and vitamin C þ E-treated skin was about 15% positive and fluorescence was less intense (Fig 4c).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The porcine skin model used in the experiments is predictive of human skin photoprotection.

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

    Findingcitation

    Addition of 0.5% ferulic acid to a topical solution of 15% L-ascorbic acid and 1% α-tocopherol improved chemical stability of the vitamins, providing more than 90% stability for L-ascorbic acid and 100% for α-tocopherol after 1 month at 45°C.

    “Its incorporation into a topical solution of 15% L-ascorbic acid and 1% a-tocopherol improved chemical stability of the vitamins (C þ E)”
    • Also stated in: § Abstract · plain
      “We have learned that addition of ferulic acid, a ubiquitous plant antioxidant, provided stability of more than 90% for L-ascorbic acid and 100% for a-tocopherol (Zielinski and Pinnell, 2004).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Zielinski and Pinnell, 2004

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingown data

    Sunburn cell counts for the combination of vitamins C, E, and ferulic acid were statistically different from control and vehicle at all MED tested and different from ferulic acid alone as well as from the combination of vitamins C+E at 2×, 4×, 6×, and 8× MED.

    “Sunburn cell counts of combination of vitamins C, E, and ferulic acid were statistically different from control and vehicle at all MED tested and different from ferulic acid alone as well as from the combination of vitamins C þ E at 2 Â , 4 Â , 6 Â , and 8 Â MED.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The porcine skin model used in the experiments is predictive of human skin photoprotection.
    • Rests on an assumption: The vehicle used does not itself affect the measured photoprotection outcomes.

  • May combine two claims.

    Findingown data

    Colorimetric measurements of erythema for the combination of vitamins C, E, and ferulic acid were statistically different from control and vehicle at all MED tested; different from ferulic acid alone at 2×, 6×, and 8× MED; and different from combination vitamins C+E at 4× and 6× MED.

    “Colorimetric measurements of combination of vitamins C, E, and ferulic acid were statistically different from control and vehicle at all minimal erythema dose (MED) tested; different from ferulic acid alone at 2 Â , 6 Â , and 8 Â MED; and different from combination vitamins C þ E at 4 Â and 6 Â MED.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The porcine skin model used in the experiments is predictive of human skin photoprotection.
    • Rests on an assumption: The vehicle used does not itself affect the measured photoprotection outcomes.

  • May combine two claims.

    Findingown data

    Activation of caspase-3 by 4× MED of solar-simulated light occurs in both epidermis and dermis; in epidermis, activation is particularly strong in the basal layer.

    “Activation occurs in both epidermis and dermis (Fig 3a-c); in epidermis, activation is particularly strong in the basal layer.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The porcine skin model used in the experiments is predictive of human skin photoprotection.
    • Rests on an assumption: Activation of caspase-3 and caspase-7 is a valid marker of apoptosis in this model.

  • May combine two claims.

    Findingown data

    The combination of 15% L-ascorbic acid, 1% α-tocopherol, and 0.5% ferulic acid provided approximately 8-fold protection and was statistically different than ferulic acid alone or the combination of vitamins C and E.

    “The combination of 15% L-ascorbic acid, 1% atocopherol, 0.5% ferulic acid provided approximately 8-fold protection and was statistically different than ferulic acid alone or the combination of vitamins C and E (Fig 1a, b).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The porcine skin model used in the experiments is predictive of human skin photoprotection.

  • The quote only partly states this claim.

    Findingown data

    Antioxidant solutions protected against activation of caspase-7 by 4× and 8× MED of solar-simulated radiation.

    “Figure 2c shows activation of caspase-7 by 4 Â and 8 Â MED of solar-simulated radiation and protection by antioxidant solutions.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The porcine skin model used in the experiments is predictive of human skin photoprotection.
    • Rests on an assumption: Activation of caspase-3 and caspase-7 is a valid marker of apoptosis in this model.

  • May combine two claims.

    Findingown data

    With 8× MED irradiation, protection of caspase-3 by vitamin C, E, and ferulic acid is almost complete and is better than vitamin C and E or ferulic acid alone.

    “With 8 Â MED of irradiation, protection of vitamin C, E, and ferulic acid is almost complete and is better than vitamin C and E or ferulic acid alone.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The porcine skin model used in the experiments is predictive of human skin photoprotection.
    • Rests on an assumption: Activation of caspase-3 and caspase-7 is a valid marker of apoptosis in this model.

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

    Findingown data

    Ferulic acid had no appreciable effect on ascorbic acid absorption.

    “It had no appreciable effect on ascorbic acid absorption (data not shown).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Both 0.5% ferulic acid alone and 15% L-ascorbic acid plus 1% α-tocopherol together provided about 4-fold protection.

    “Both 0.5% ferulic acid alone and 15% L-ascorbic acid þ 1% a-tocopherol together provided about 4-fold protection (Fig 1a, b).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The porcine skin model used in the experiments is predictive of human skin photoprotection.

  • May combine two claims.

    Findingown data

    Ferulic acid alone and vitamins C+E provide partial protection against caspase-3 activation, but vitamins C, E, and ferulic acid provide virtually complete protection.

    “Ferulic acid alone (3b) and vitamins C þ E (3c) provide partial protection but vitamins C, E, and ferulic acid (3d) provides virtually complete protection.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The porcine skin model used in the experiments is predictive of human skin photoprotection.
    • Rests on an assumption: Activation of caspase-3 and caspase-7 is a valid marker of apoptosis in this model.

  • May combine two claims.

    Premisecitation

    Sun protection factor is measured at 2 mg per cm2, yet in actual use, sunscreen application is only 0.4-0.5 mg per cm2.

    “Sun protection factor is measured at 2 mg per cm 2 , yet in actual use, sunscreen application is only 0.4-0.5 mg per cm 2 (Wulf et al, 1997;Autier et al, 2001).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Wulf et al, 1997 source
    • cites Autier et al, 2001 source

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

    Premisecitation

    Approximately one third of UVA-induced oxidative stress in skin occurs at the surface of skin.

    “Approximately one third of UVA-induced oxidative stress in skin occurs at the surface of skin (Ou-Yang et al, 2004).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ou-Yang et al, 2004 source

  • May combine two claims.

    Premisenone given

    SPF is a measurement of UVB only and reveals nothing about UVA photoprotection.

    “In addition, SPF is a measurement of UVB only and reveals nothing about UVA photoprotection, protection necessary to protect against oxidative stress.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    With daily oral supplements of 3 g vitamin C and 2 g vitamin E, protection against photodamage in skin is increased approximately 1.5 times; either vitamin alone is ineffective.

    “With daily oral supplements of 3 g vitamin C and 2 g vitamin E, protection against photodamage in skin is increased approximately 1.5 times; either vitamin alone is ineffective (Fuchs and Kern, 1998).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Fuchs and Kern, 1998 source

  • May combine two claims.

    Premisecitation

    Ferulic acid is a potent antioxidant with synergistic interactions with ascorbic acid.

    “Ferulic acid is a potent antioxidant with synergistic interactions with ascorbic acid (Trombino et al, 2004).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Trombino et al, 2004 source

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

    Premisecitation

    Ferulic acid absorbs UV radiation with an absorption maximum at 307 nm (log e = 4.19).

    “Ferulic acid absorbs UV radiation with an absorption maximum at 307 nm (log e ¼ 4.19) (Graf, 1992).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Graf, 1992 source

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

    Premisecitation

    Ferulic acid is a potent phenolic antioxidant found ubiquitously and at high concentrations in plants.

    “Ferulic acid is a potent phenolic antioxidant found ubiquitously and at high concentrations in plants (Graf, 1992;Rice-Evans et al, 1996;Ou and Kwok, 2004).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Graf, 1992 source
    • cites Rice-Evans et al, 1996 source
    • cites Ou and Kwok, 2004 source

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

    Study design and conductnone given

    Experiments were performed on weanling white Yorkshire pigs in accord with guidelines prepared by the Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Resources, National Research Council.

    “Experiments were performed on weanling white Yorkshire pigs in accord with the guidelines prepared by the Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Resources, National Research Council (National Institutes of Health, publication No. 86-23, revised 1996).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Fifteen percent L-ascorbic acid saturates skin in 3 d; its tissue half-life is about 4 d.

    “Fifteen percent L-ascorbic acid saturates skin in 3 d; its tissue half life is about 4 d (Pinnell et al, 2001).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Pinnell et al, 2001 source

  • May combine two claims.

    Premisecitation

    Vitamins C and E interact synergistically to protect each other and increase overall effectiveness.

    “Vitamins C and E interact synergistically to protect each other and increase overall effectiveness (Pinnell et al, 2001).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Pinnell et al, 2001 source
21 of 21

  • The paper relies on this without support.

    The porcine skin model used in the experiments is predictive of human skin photoprotection.

    “Experiments were performed on weanling white Yorkshire pigs in accord with the guidelines prepared by the Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Resources, National Research Council (National Institutes of Health, publication No. 86-23, revised 1996).”

  • The paper relies on this without support.

    Activation of caspase-3 and caspase-7 is a valid marker of apoptosis in this model.

    “In an effort to explore the mechanism of apoptosis in these experiments, western blots were carried out to determine levels of caspase-3 and its downstream effector, caspase-7.”

  • The paper relies on this without support.

    The vehicle used does not itself affect the measured photoprotection outcomes.

    “Skin was pretreated with vehicle, 0.5% ferulic acid, 15% vitamin C and 1% vitamin E, 15% vitamin C and 1% vitamin E, and 0.5% ferulic acid and irradiated with solar-simulated radiation 2 Â to 10 Â minimal erythema dose (MED) at 2 Â MED intervals.”

  • The paper relies on this without support.

    Chemical stability at 45°C for 1 month predicts stability under normal storage conditions.

    “Chemical stability was determined after 1 mo at 451C.”
4 of 4

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?

  • Topical CEFer may protect against photoaging and skin cancers.

    “This suggests a role for topical CEFer in protecting against photoaging and skin cancers [64, 65].”

    From Sunscreens and Photoaging: A Review of Current Literature (2021) · cites this paper as [64]

  • Vitamin C is not synthesized by the human body and must be replenished via oral intake.

    “It is not synthesized by the human body and must be replenished via oral intake [64].”

    From Sunscreens and Photoaging: A Review of Current Literature (2021) · cites this paper as [64]

  • A stable formulation of vitamin C can be made by compounding it with vitamin E (alpha-tocopherol) and ferulic acid.

    “a stable formulation can be made by compounding it with other antioxidants: vitamin E (alpha-tocopherol) and ferulic acid [61, 64].”

    From Sunscreens and Photoaging: A Review of Current Literature (2021) · cites this paper as [64]

Cites

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Related

Authors
Lin, F.-H., Lin, J.-Y., Gupta, R. D., Tournas, J. A., Burch, J. A., Angelica Selim, M., Monteiro-Riviere, N. A., Grichnik, J. M., Zielinski, J., & Pinnell, S. R.
Affiliations
  • Duke Medical Center (US)
  • Chang Gung Memorial Hospital (TW)
  • North Carolina State University (US)
Corresponding author
Pinnell, Sheldon R.
ORCID
Venue
Journal of Investigative Dermatology
Publisher
Elsevier BV
Published
2005-10
Volume
125
Issue
4
Pages
826-832
ISSN
0022-202X (ISSN-L)
DOI
10.1111/j.0022-202x.2005.23768.x
OpenAlex
W2139034283
Cited by
365
References
45
Citations by year
2026: 27 · 2025: 26 · 2024: 17 · 2023: 24 · 2022: 30 · 2021: 26 · 2020: 15 · 2019: 19 · 2018: 14 · 2017: 19 · 2016: 19 · 2015: 23 · 2014: 10 · 2013: 11 · 2012: 19
FWCI
11.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Investigative Dermatology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (1r43ca083538-01a1)
  • National Cancer Institute (R43 CA 83538)
Topics
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
  • Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
Keywords
ferulic acid, vitamin C, vitamin E, topical antioxidants, photoprotection, skin, chemical stability, erythema, sunburn cells, apoptosis, caspase-3, caspase-7, thymine dimers, oxidative stress, photoaging, skin cancer prevention
MeSH terms
Animals, Ascorbic Acid, Coumaric Acids, Drug Stability, Radiation-Protective Agents, Swine, Ultraviolet Rays, Vitamin E, Skin Aging

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