J Cosmet Med 2022; 6(2): 67-71
Published online December 31, 2022
Cheuk Hung Lee, MBBS (HK), FHKAM (MED), FHKCP, MScPD (Cardiff), MRCP (UK), DPD (Wales), DipDerm (Glasgow), PGDipClinDerm (London), MRCP (London), GradDipDerm (NUS), DipMed (CUHK)1 , Kar Wai Alvin Lee, MBChB (CUHK), DCH (Sydney), Dip Derm (Glasgow), MScClinDerm (Cardiff), MScPD (Cardiff), DipMed (CUHK), DCH (Sydney)1 , Kwin Wah Chan, MBChB (CUHK), MScPD (Cardiff), PgDipPD (Cardiff), PGDipClinDerm (Lond), DipMed (CUHK), DCH (Sydney)1 , Kar Fai Victor Lee, MBBS, MRCP (UK), FRCP (Glasgow), FHKCP, FHKAM (Medicine)2 , Kar Wai Phoebe Lam, MBCHB (OTAGO), MRCS (EDIN), MSCPD (CARDIFF)3
1Ever Keen Medical Centre, Hong Kong
2London Heart Practice, Hong Kong
3Perfect Skin Solution, Hong Kong
Correspondence to :
Kar Wai Alvin Lee
E-mail: alvin429@yahoo.com
© Korean Society of Korean Cosmetic Surgery & Medicine
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Photoaging is a process of normal skin architecture damage caused by ultraviolet radiation. Topical vitamins have been used to treat these conditions. The authors aimed to understand the mechanism and level of evidence of topical vitamins used to treat photodamaged skin. A range of topical vitamins has been used in cosmetic medicine for many years to treat photodamaged skin. This review article compares their efficacy and level of evidence. This study was a systematic review to evaluate the efficacy of different topical vitamins. Keywords including “Photoaging,” “Botanicals,” “Peptides,” “Retinoids,” “Vitamins” were searched on Ovid, PubMed, MEDLINE for relevant studies published on photoaging treatment. There is a wealth of Level I evidence supporting the use of topical retinoic acid, vitamins B and C. There is evidence supporting the use of topical vitamin E although it is mainly drawn from Level IV studies of the evidence hierarchy. Topical vitamins can effectively treat photodamaged skin.
Level of Evidence: I
Keywords: ascorbic acid, niacinamide, retinoids, skin aging, tocopherols, vitamins
The process of damage to normal skin architecture caused by ultraviolet light is called photoaging. It is associated with a series of histological changes, including uneven basal melanocyte distribution (irregular dyspigmentation), cytological atypia, reduction of Langerhans cells, elastic fibers, dermal collagen degeneration, increment of dermal inflammatory cells, and increased epidermal thickness variability. Furthermore, dermal elastosis is also observed in photoaging, which is caused by abnormal amorphous elastic material deposition in the papillary dermis [1,2].
With the advent of topical vitamins, they provide a novel and non-invasive way to rejuvenate photodamaged skin.
This systematic review article summarizes topical vitamin treatment of photoaging.
Keywords including “Photoaging,” “Botanicals,” “Peptides,” “Retinoids,” and “Vitamins” were searched in the Ovid, PubMed, and MEDLINE databases for relevant studies published on photoaging treatment. Some papers were further reviewed using objective endpoint measurements, a double-blinding approach, control usage, randomization usage, and sample size. All studies were classified according to the Oxford Center for evidence-based medicine evidence hierarchy (Fig. 1) [3].
Through the production of types I and III procollagen, transforming growth factor-β (TGF-β) induction has been observed by topical trans-retinoic acid application to mouse and human skin [4,5]. In photoaged human skin, increased collagen fibril deposition is observed since all trans-retinoic acid can promote types I and III procollagen gene expression [6]. Kligman et al. [7] compared topical retinoic acid with a placebo for skin repair promotion in mouse skin after ultraviolet irradiation. The retinoic acid group had a larger reconstruction zone than that of the placebo group. Griffiths et al. [8] enrolled 29 photodamaged patients treated with 0.1% tretinoin versus vehicle cream. In the control group, collagen was reduced by 14%, whereas collagen I production increased by 80%, as confirmed by immunohistological assessment (Level IIb).
Kang et al. [9] enrolled 568 photodamaged patients in their study, which was placebo-controlled, double-blinded, randomized, and multi-center. A 0.1% tazarotene was used against vehicle cream (control) and showed that 0.1% tazarotene significantly decreased elastosis, dyspigmentation, and fine wrinkles (Level Ib). Bhawan et al. [10] also involved 533 patients in another placebo-controlled, double-blind, randomized controlled study on topical retinoid effectiveness in photoaging. They showed that patients’ skin had increased granular layer thickness and melanin content reduction compared to vehicle cream, as shown by computerized images and histological analyses (Level Ib). Another large study was conducted by Weinstein et al. [11], who enrolled 251 mild-to-moderated photodamaged patients. In this multi-center, vehicle-controlled, randomized controlled study, we used 0.05% topical tretinoin versus vehicle cream. The researchers analyzed the results by assessing the histological structure, which showed melanin reduction and epidermal thickness (Level Ib). A subjective assessment revealed a decrease in roughness, laxity, mottled pigmentation, and wrinkling. A review was performed by the Cochrane collaboration on eight controlled trials on the effect of topical retinoids on photodamaged skin [12], with topical isotretinoin (0.1%), topical tazarotene (0.01%–0.1%), and topical tretinoin cream (0.02% or higher concentration) showing that photodamaged skin significantly improved with their usage (Level Ia).
Creidi et al. [13] enrolled 120 photodamaged patients in a randomized controlled study to compare the effectiveness of topical retinoids with vehicle cream. Using optical profilometry techniques, the left crow’s feet area silicone replica was analyzed. The team found that skin roughness and rhytides were significantly reduced in the retinoid treatment group (Level IIb).
Griffiths et al. [8] also demonstrated that tretinoin cream could significantly increase vascularity and epidermal thickening in randomized controlled, vehicle-controlled, and double-blind studies. Two concentrations of tretinoin cream (0.025% and 0.1%) were used in comparison with the vehicle cream to treat photodamaged skin for 48 weeks (Level Ib).
In summary, with preclinical research demonstrating clear molecular mechanisms and multiple Level I evidence, retinoic acid (vitamin A) is very effective in treating photodamaged skin.
Kawada et al. [14] enrolled 30 patients with periorbital rhytides in their study to analyze the effect of 4% nicotinamide cream. This was a placebo-controlled and randomized controlled split-face study. Through objective and subjective computer analyses, 4% nicotinamide cream showed significantly decreased rhytides compared to that of vehicle cream. This study was unblinded, but the level of evidence was not low (Level Ib). Bissett et al. [15] included 50 patients in their split-face randomized controlled study to compare the effectiveness of topical nicotinamide cream with that of the control cream. Reduction of sallowness, erythema, hyperpigmentation, and rhytides was statistically significant when compared to the control cream (Level Ib).
Ten photodamaged patients were enrolled in the split-face double-blind controlled study by Fitzpatrick and Rostan [16] in 2002. The effectiveness of topical vitamin C was compared with that of placebo cream. Histologically, the skin area treated with topical vitamin C showed increased type I collagen and Granz zone collagen. Furthermore, clinical investigators have also assessed and found improvements in skin inflammation, pigmentation, hydration, and wrinkle scores. Although few patients were included, the level of evidence was not low (Level Ib). Traikovich [17] also analyzed the effectiveness of vitamin C in photoaging using 10% ascorbic acid. They enrolled 19 photoaging patients in their study, which was designed as vehicle-controlled, double-blind, and randomized controlled. The study period was 3 months, with vehicle cream used as the control cream. Using skin surface topography computer-assisted image analysis and optical profilometry, the team found significant improvements in overall features, yellowing/sallowness, coarse wrinkles, tactile roughness, and fine rhytides (Level Ib).
Interestingly, most clinical studies analyzing topical vitamin E were involved with topical vitamin C. Lin et al. [18] used the skin of pigs to compare the photoprotective effect of topical vitamins C and E, versus topical vitamin C, versus topical vitamin E. The team concluded that the best photoprotective effect was a combination of topical vitamins C and E. Nevertheless, topical vitamins C and E alone could also lower thymine dimers, sunburn cells, and erythema with ultraviolet (UV) irradiation (Level IV). Eberlein-König et al. [19] enrolled 20 photoaged patients in a placebo-controlled, double-blinded study to analyze the photoprotective effects of topical vitamins C and E. In response to sunlight, after 8 days of treatment, there was an increment in the minimal erythema dose (the minimal ultraviolet light dose induced cutaneous blood flow together with erythematous response), while in the control group, the dose was reduced (Level IIb).
Only one pharmaceutical agent has a large evidence base for use in photoaging. It is a retinoid (vitamin A).
Retinoids are β-carotene derivatives. By binding promoter DNA sequences, retinoic acid influences the expression of genes encoding active chemicals after oxidation and hydrolysis of beta-carotene and its metabolites. Retinoids cause pigment loss and inhibit tyrosinase and matrix metalloproteinases through epidermopoiesis. They can also increase the amount of dermal collagen through the synthesis of TGF-β procollagen and stimulation of water content (by stimulating glycosaminoglycan synthesis). Furthermore, they exhibit antioxidant properties and UV light-absorbing features [20].
Vitamin B3 (niacinamide or nicotinamide) and vitamin B5 (Panthenol) have good pharmacological effects on photoaging skin. nicotinamide adenine dinucleotide phosphate, nicotinamide adenine dinucleotide, and nicotinamide adenine dinucleotide phosphate hydrogen are antioxidants derived from the reduction of nicotinamide adenine dinucleotide. They can decrease the glycation of proteins (skin yellowness causation), inhibit the transfer of melanosomes, and decrease transepidermal loss of water. Vitamin B5 is related to coenzyme A, which is its precursor and plays an important role in multiple metabolic pathways. It affects the rehydration of the skin, enhancement of re-epithelialization of the epidermis, and proliferation of fibroblasts [21].
Vitamin C, also known as l-ascorbic acid, has a powerful therapeutic effect on photoaging skin. Its mechanism involves neutralizing free radicals by donating electrons, which reduce the damage to cells, dermal collagen, and DNA, which are the mediators of photodamage. It also reduces pigmentation by L-dopaquinone depletion (melanin precursor) and stimulates collagen synthesis during collagen cross-linking. Furthermore, it stabilizes collagen by acting as a co-factor for lysyl and prolyl hydroxylases [22].
Vitamin E is an antioxidant and the most abundant form is alpha-tocopherol. In response to ultraviolet light, it can decrease the risk of carcinogenesis, rhytide formation, and erythema of the skin. It reduces skin ultrastructural oxidative damage by scavenging lipid peroxyl radicals [23].
There is a wealth of Level I evidence supporting the use of topical retinoic acid, vitamin B, and vitamin C. Evidence supporting the use of topical vitamin E is mainly drawn from studies from Level IV of the evidence hierarchy.
The authors have nothing to disclose.
J Cosmet Med 2022; 6(2): 67-71
Published online December 31, 2022 https://doi.org/10.25056/JCM.2022.6.2.67
Copyright © Korean Society of Korean Cosmetic Surgery & Medicine.
Cheuk Hung Lee, MBBS (HK), FHKAM (MED), FHKCP, MScPD (Cardiff), MRCP (UK), DPD (Wales), DipDerm (Glasgow), PGDipClinDerm (London), MRCP (London), GradDipDerm (NUS), DipMed (CUHK)1 , Kar Wai Alvin Lee, MBChB (CUHK), DCH (Sydney), Dip Derm (Glasgow), MScClinDerm (Cardiff), MScPD (Cardiff), DipMed (CUHK), DCH (Sydney)1 , Kwin Wah Chan, MBChB (CUHK), MScPD (Cardiff), PgDipPD (Cardiff), PGDipClinDerm (Lond), DipMed (CUHK), DCH (Sydney)1 , Kar Fai Victor Lee, MBBS, MRCP (UK), FRCP (Glasgow), FHKCP, FHKAM (Medicine)2 , Kar Wai Phoebe Lam, MBCHB (OTAGO), MRCS (EDIN), MSCPD (CARDIFF)3
1Ever Keen Medical Centre, Hong Kong
2London Heart Practice, Hong Kong
3Perfect Skin Solution, Hong Kong
Correspondence to:Kar Wai Alvin Lee
E-mail: alvin429@yahoo.com
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Photoaging is a process of normal skin architecture damage caused by ultraviolet radiation. Topical vitamins have been used to treat these conditions. The authors aimed to understand the mechanism and level of evidence of topical vitamins used to treat photodamaged skin. A range of topical vitamins has been used in cosmetic medicine for many years to treat photodamaged skin. This review article compares their efficacy and level of evidence. This study was a systematic review to evaluate the efficacy of different topical vitamins. Keywords including “Photoaging,” “Botanicals,” “Peptides,” “Retinoids,” “Vitamins” were searched on Ovid, PubMed, MEDLINE for relevant studies published on photoaging treatment. There is a wealth of Level I evidence supporting the use of topical retinoic acid, vitamins B and C. There is evidence supporting the use of topical vitamin E although it is mainly drawn from Level IV studies of the evidence hierarchy. Topical vitamins can effectively treat photodamaged skin.
Level of Evidence: I
Keywords: ascorbic acid, niacinamide, retinoids, skin aging, tocopherols, vitamins
The process of damage to normal skin architecture caused by ultraviolet light is called photoaging. It is associated with a series of histological changes, including uneven basal melanocyte distribution (irregular dyspigmentation), cytological atypia, reduction of Langerhans cells, elastic fibers, dermal collagen degeneration, increment of dermal inflammatory cells, and increased epidermal thickness variability. Furthermore, dermal elastosis is also observed in photoaging, which is caused by abnormal amorphous elastic material deposition in the papillary dermis [1,2].
With the advent of topical vitamins, they provide a novel and non-invasive way to rejuvenate photodamaged skin.
This systematic review article summarizes topical vitamin treatment of photoaging.
Keywords including “Photoaging,” “Botanicals,” “Peptides,” “Retinoids,” and “Vitamins” were searched in the Ovid, PubMed, and MEDLINE databases for relevant studies published on photoaging treatment. Some papers were further reviewed using objective endpoint measurements, a double-blinding approach, control usage, randomization usage, and sample size. All studies were classified according to the Oxford Center for evidence-based medicine evidence hierarchy (Fig. 1) [3].
Through the production of types I and III procollagen, transforming growth factor-β (TGF-β) induction has been observed by topical trans-retinoic acid application to mouse and human skin [4,5]. In photoaged human skin, increased collagen fibril deposition is observed since all trans-retinoic acid can promote types I and III procollagen gene expression [6]. Kligman et al. [7] compared topical retinoic acid with a placebo for skin repair promotion in mouse skin after ultraviolet irradiation. The retinoic acid group had a larger reconstruction zone than that of the placebo group. Griffiths et al. [8] enrolled 29 photodamaged patients treated with 0.1% tretinoin versus vehicle cream. In the control group, collagen was reduced by 14%, whereas collagen I production increased by 80%, as confirmed by immunohistological assessment (Level IIb).
Kang et al. [9] enrolled 568 photodamaged patients in their study, which was placebo-controlled, double-blinded, randomized, and multi-center. A 0.1% tazarotene was used against vehicle cream (control) and showed that 0.1% tazarotene significantly decreased elastosis, dyspigmentation, and fine wrinkles (Level Ib). Bhawan et al. [10] also involved 533 patients in another placebo-controlled, double-blind, randomized controlled study on topical retinoid effectiveness in photoaging. They showed that patients’ skin had increased granular layer thickness and melanin content reduction compared to vehicle cream, as shown by computerized images and histological analyses (Level Ib). Another large study was conducted by Weinstein et al. [11], who enrolled 251 mild-to-moderated photodamaged patients. In this multi-center, vehicle-controlled, randomized controlled study, we used 0.05% topical tretinoin versus vehicle cream. The researchers analyzed the results by assessing the histological structure, which showed melanin reduction and epidermal thickness (Level Ib). A subjective assessment revealed a decrease in roughness, laxity, mottled pigmentation, and wrinkling. A review was performed by the Cochrane collaboration on eight controlled trials on the effect of topical retinoids on photodamaged skin [12], with topical isotretinoin (0.1%), topical tazarotene (0.01%–0.1%), and topical tretinoin cream (0.02% or higher concentration) showing that photodamaged skin significantly improved with their usage (Level Ia).
Creidi et al. [13] enrolled 120 photodamaged patients in a randomized controlled study to compare the effectiveness of topical retinoids with vehicle cream. Using optical profilometry techniques, the left crow’s feet area silicone replica was analyzed. The team found that skin roughness and rhytides were significantly reduced in the retinoid treatment group (Level IIb).
Griffiths et al. [8] also demonstrated that tretinoin cream could significantly increase vascularity and epidermal thickening in randomized controlled, vehicle-controlled, and double-blind studies. Two concentrations of tretinoin cream (0.025% and 0.1%) were used in comparison with the vehicle cream to treat photodamaged skin for 48 weeks (Level Ib).
In summary, with preclinical research demonstrating clear molecular mechanisms and multiple Level I evidence, retinoic acid (vitamin A) is very effective in treating photodamaged skin.
Kawada et al. [14] enrolled 30 patients with periorbital rhytides in their study to analyze the effect of 4% nicotinamide cream. This was a placebo-controlled and randomized controlled split-face study. Through objective and subjective computer analyses, 4% nicotinamide cream showed significantly decreased rhytides compared to that of vehicle cream. This study was unblinded, but the level of evidence was not low (Level Ib). Bissett et al. [15] included 50 patients in their split-face randomized controlled study to compare the effectiveness of topical nicotinamide cream with that of the control cream. Reduction of sallowness, erythema, hyperpigmentation, and rhytides was statistically significant when compared to the control cream (Level Ib).
Ten photodamaged patients were enrolled in the split-face double-blind controlled study by Fitzpatrick and Rostan [16] in 2002. The effectiveness of topical vitamin C was compared with that of placebo cream. Histologically, the skin area treated with topical vitamin C showed increased type I collagen and Granz zone collagen. Furthermore, clinical investigators have also assessed and found improvements in skin inflammation, pigmentation, hydration, and wrinkle scores. Although few patients were included, the level of evidence was not low (Level Ib). Traikovich [17] also analyzed the effectiveness of vitamin C in photoaging using 10% ascorbic acid. They enrolled 19 photoaging patients in their study, which was designed as vehicle-controlled, double-blind, and randomized controlled. The study period was 3 months, with vehicle cream used as the control cream. Using skin surface topography computer-assisted image analysis and optical profilometry, the team found significant improvements in overall features, yellowing/sallowness, coarse wrinkles, tactile roughness, and fine rhytides (Level Ib).
Interestingly, most clinical studies analyzing topical vitamin E were involved with topical vitamin C. Lin et al. [18] used the skin of pigs to compare the photoprotective effect of topical vitamins C and E, versus topical vitamin C, versus topical vitamin E. The team concluded that the best photoprotective effect was a combination of topical vitamins C and E. Nevertheless, topical vitamins C and E alone could also lower thymine dimers, sunburn cells, and erythema with ultraviolet (UV) irradiation (Level IV). Eberlein-König et al. [19] enrolled 20 photoaged patients in a placebo-controlled, double-blinded study to analyze the photoprotective effects of topical vitamins C and E. In response to sunlight, after 8 days of treatment, there was an increment in the minimal erythema dose (the minimal ultraviolet light dose induced cutaneous blood flow together with erythematous response), while in the control group, the dose was reduced (Level IIb).
Only one pharmaceutical agent has a large evidence base for use in photoaging. It is a retinoid (vitamin A).
Retinoids are β-carotene derivatives. By binding promoter DNA sequences, retinoic acid influences the expression of genes encoding active chemicals after oxidation and hydrolysis of beta-carotene and its metabolites. Retinoids cause pigment loss and inhibit tyrosinase and matrix metalloproteinases through epidermopoiesis. They can also increase the amount of dermal collagen through the synthesis of TGF-β procollagen and stimulation of water content (by stimulating glycosaminoglycan synthesis). Furthermore, they exhibit antioxidant properties and UV light-absorbing features [20].
Vitamin B3 (niacinamide or nicotinamide) and vitamin B5 (Panthenol) have good pharmacological effects on photoaging skin. nicotinamide adenine dinucleotide phosphate, nicotinamide adenine dinucleotide, and nicotinamide adenine dinucleotide phosphate hydrogen are antioxidants derived from the reduction of nicotinamide adenine dinucleotide. They can decrease the glycation of proteins (skin yellowness causation), inhibit the transfer of melanosomes, and decrease transepidermal loss of water. Vitamin B5 is related to coenzyme A, which is its precursor and plays an important role in multiple metabolic pathways. It affects the rehydration of the skin, enhancement of re-epithelialization of the epidermis, and proliferation of fibroblasts [21].
Vitamin C, also known as l-ascorbic acid, has a powerful therapeutic effect on photoaging skin. Its mechanism involves neutralizing free radicals by donating electrons, which reduce the damage to cells, dermal collagen, and DNA, which are the mediators of photodamage. It also reduces pigmentation by L-dopaquinone depletion (melanin precursor) and stimulates collagen synthesis during collagen cross-linking. Furthermore, it stabilizes collagen by acting as a co-factor for lysyl and prolyl hydroxylases [22].
Vitamin E is an antioxidant and the most abundant form is alpha-tocopherol. In response to ultraviolet light, it can decrease the risk of carcinogenesis, rhytide formation, and erythema of the skin. It reduces skin ultrastructural oxidative damage by scavenging lipid peroxyl radicals [23].
There is a wealth of Level I evidence supporting the use of topical retinoic acid, vitamin B, and vitamin C. Evidence supporting the use of topical vitamin E is mainly drawn from studies from Level IV of the evidence hierarchy.
The authors have nothing to disclose.
Cheuk Hung Lee, MBBS (HK), FHKAM (MED), FHKCP, MScPD (Cardiff), MRCP (UK), DPD (Wales), DipDerm (Glasgow), PGDipClinDerm (London), MRCP (London), GradDipDerm (NUS), DipMed (CUHK), Kar Wai Alvin Lee, MBChB (CUHK), DCH (Sydney), Dip Derm (Glasgow), MScClinDerm (Cardiff), MScPD (Cardiff), DipMed (CUHK), DCH (Sydney), Lisa Kwin Wah Chan, MBChB (CUHK), MScPD (Cardiff), PgDipPD (Cardiff), PGDipClinDerm (Lond), DipMed (CUHK), DCH (Sydney), Kar Fai Victor Lee, MBBS (UCL, University of London), MRCP (UK), FRCP (Glasgow), FHKCP, FHKAM (Medicine)
J Cosmet Med 2023; 7(1): 1-5 https://doi.org/10.25056/JCM.2023.7.1.1Preamjit Saonanon, MD , Krit Rattanakit, MD , Patnapa Vejanurug, MD , Apichaya Thanyavuthi, MD
J Cosmet Med 2021; 5(1): 30-35 https://doi.org/10.25056/JCM.2021.5.1.30