Article

Niacinamide: A B Vitamin that Improves Aging Facial Skin Appearance

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

In multiple chronic clinical studies, topical niacinamide (vitamin B3) has been observed to be well tolerated by skin and to provide a broad array of improvements in the appearance of aging facial skin (eg, reduction in the appearance of hyperpigmentated spots and red blotchiness). To clinically determine the effect of topical niacinamide on additional skin appearance and property end points (wrinkles, yellowing, and elasticity). Female white subjects (N = 50) with clinical signs of facial photoaging (fine lines and wrinkles, poor texture, and hyperpigmented spots) applied 5% niacinamide to half of the face and its vehicle control to the other half twice daily for 12 weeks (double blind, left-right randomized). Facial images and instrumental measures were obtained at baseline and at 4-week intervals. Analyses of the data revealed a variety of significant skin appearance improvement effects for topical niacinamide: reductions in fine lines and wrinkles, hyperpigmented spots, red blotchiness, and skin sallowness (yellowing). In addition, elasticity (as measured via cutometry) was improved. Corresponding mechanistic information is presented. In addition to previously observed benefits for topical niacinamide, additional effects were identified (improved appearance of skin wrinkles and yellowing and improved elasticity).

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... 24 In clinical trials, a significant improvement in skin appearance, including reductions in fine lines and wrinkles, hyperpigmented spots, red blotchiness and skin sallowness, as well as improved elasticity was found following application of 5% niacinamide for 12 weeks in Caucasian women. 25,26 In another clinical trial, application of 4% niacinamide in Japanese women for 8 weeks resulted in a significant decrease in wrinkles and skin roughness. 27 The antiwrinkling effects of niacinamide may be explained by the fact that niacinamide increases collagen production, 24 an effect that is also relevant to other antiwrinkle agents, such as all-trans retinoic acid. ...
... 29 Niacinamide also modulates yellowing (sallowness) of the skin by an inhibition of protein glycation via antioxidant effects. 25,26 Niacinamide increases both the lipid (ceramide) and protein (keratin, involucrin, filaggrin) components of the skin barrier and enhances the skin barrier properties, which may improve red blotchiness. 30,31 Further, niacinamide has been demonstrated to inhibit melanosome transfer from melanocytes to keratinocytes and promote skin lightening in vivo. ...
... 32 The mechanism by which elasticity improves is not defined, but dermal remodeling (as evidenced by the observed increases in skin collagen) and prevention of dermal matrix glycation may be contributory factors. 25,26 Other ingredients present in the test products for their anti-inflammatory properties which help to soothe sensitive skin and for their potential to combat skin aging include Avena sativa (oat) kernel extract, disodium lauriminodipropionate tocopheryl phosphates (a form of vitamin E) and Hamamelis virginiana (witch hazel) water. Oat avenanthramides are known to suppress histamine release at very low doses, helping to plump up the skin, reduce wrinkles, and restore the skin natural barrier. ...
Article
Full-text available
Background: Sensitive skin affects an increasingly large proportion of the population and is less tolerant to frequent and prolonged use of cosmetics. This study investigates the antiaging effects of a skin care system developed for use on sensitive skin. Methods: A total of 30 healthy Caucasian females, aged 32-72, were enrolled in this double-blind randomized placebo-controlled split-face study. A routine consisting of twice daily topical applications of the test cleanser and test moisturizer or placebo or positive control products was followed for 28 days, with parameters measured at baseline and at 7-day intervals. Objective skin assessments for hydration, transepidermal water loss (TEWL), skin surface topography, elasticity and safety assessment were conducted. Results: Wrinkle surface, length and depth significantly improved by 34.8±4.7% (P<0.001), 19.0±3.2% (P<0.05) and 24.3±3.5% (P<0.05), respectively, after 28 days of skin care treatment with the test cleanser and test moisturizer. R2 (gross elasticity), R5 (net elasticity) and R7 (biological elasticity) significantly increased by 32.8±6.5% (P<0.001), 47.3±8.6% (P<0.001) and 50.6±5.1% (P<0.001), respectively, while R6 (viscoelastic portion) significantly decreased by 33.4±4.6% (P<0.001) after 28 days. Skin hydration was also found to increase significantly after 28 days by 42.2±8.5% (P<0.01), but there was no change in TEWL. No adverse events were reported. Conclusions: A novel skin care routine developed for use on sensitive skin significantly improves the signs of aging including hydration, wrinkle size and elasticity without significant adverse effects.
... In the field of dermatology, many studies on nicotinamide and its analogs have been reported concerning the prevention and treatment of cancer, blistering disorders, acne vulgaris, psoriasis, wound healing, and pigmentation disorders [18][19][20][21]. Nicotinamide has also been used in the cosmetic field for decades to prevent skin aging and brighten skin tone [22][23][24][25]. However, its mechanism of action in alleviating skin diseases or controlling skin aging and pigmentation is not well understood. ...
... Clinical studies on the skin antiaging efficacy of nicotinamide alone or in combination with other active ingredients are summarized in Table 1. In double-blind, placebocontrolled, split-face, left-right, randomized clinical studies, Bissett et al. assessed the effect of nicotinamide on the appearance of aging facial skin [23,24]. Moisturizer product with or without containing 5% nicotinamide was applied on the facial skin for 12 weeks. ...
... 5% nicotinamide [24] A double-blind, placebo formulation-controlled, split-face study with left-right randomization 50 ...
Article
Full-text available
Vitamin B3 (nicotinic acid, niacin) deficiency causes the systemic disease pellagra, which leads to dermatitis, diarrhea, dementia, and possibly death depending on its severity and duration. Vitamin B3 is used in the synthesis of the NAD+ family of coenzymes, contributing to cellular energy metabolism and defense systems. Although nicotinamide (niacinamide) is primarily used as a nutritional supplement for vitamin B3, its pharmaceutical and cosmeceutical uses have been extensively explored. In this review, we discuss the biological activities and cosmeceutical properties of nicotinamide in consideration of its metabolic pathways. Supplementation of nicotinamide restores cellular NAD+ pool and mitochondrial energetics, attenuates oxidative stress and inflammatory response, enhances extracellular matrix and skin barrier, and inhibits the pigmentation process in the skin. Topical treatment of nicotinamide, alone or in combination with other active ingredients, reduces the progression of skin aging and hyperpigmentation in clinical trials. Topically applied nicotinamide is well tolerated by the skin. Currently, there is no convincing evidence that nicotinamide has specific molecular targets for controlling skin aging and pigmentation. This substance is presumed to contribute to maintaining skin homeostasis by regulating the redox status of cells along with various metabolites produced from it. Thus, it is suggested that nicotinamide will be useful as a cosmeceutical ingredient to attenuate skin aging and hyperpigmentation, especially in the elderly or patients with reduced NAD+ pool in the skin due to internal or external stressors.
... In a double-blind, randomized, controlled trial 5% NAM cream was applied twice daily for 12 weeks to half of the face, and its vehicle control to the other half of the face, of 50 Caucasian women. NAM treatment significantly improved skin appearance by reducing signs of aging, including reductions in fine lines and wrinkles, hyperpigmented spots, red blotchiness, and skin sallowness, and it improved skin elasticity [77]. Another double-blind, split-face, randomized controlled study was performed in 30 healthy Japanese females. ...
... NAM reduces skin cancer incidence and prevents the immune-suppressive effects of UV radiation in mice when given topically or orally [72,73]. Furthermore, clinical studies have shown that topical use of NAM reduced skin aging signs [77][78][79][80]. Oral NAM administration reduces the level of immunosuppression induced by UV radiation without altering baseline immunity and it lowers the rate of NMSCs, including AKs. ...
Article
Full-text available
Nicotinamide (NAM) is an amide form of vitamin B3 and the precursor of nicotinamide adenine dinucleotide (NAD+), an essential co-enzyme of redox reactions for adenosine triphosphate (ATP) production and for other metabolic processes. As NAD+ status is critical in maintaining cellular energy, vitamin B3 deficiency mainly affects tissues that need high cellular energy causing pellagra and skin sun sensitivity. In animal models, NAD+ deficiency leads to UV sensitivity of the skin, impairs DNA damage response, and increases genomic instability and cancer incidence. Furthermore, NAD+ depletion is associated with human skin aging and cancer. NAM prevents the UV-induced ATP depletion boosting cellular energy and enhances DNA repair activity in vitro and in vivo. Moreover, NAM reduces skin cancer incidence and prevents the immune-suppressive effects of UV in mice. Thus, NAM is involved in the maintenance of genomic stability and may have beneficial effects against skin aging changes and tumor development. Clinical studies showed that topical use of NAM reduces cutaneous aging. Furthermore, oral NAM administration reduces the level of UV-mediated immunosuppression and lowers the rate of non-melanoma skin cancers in high-risk patients. Therefore, NAM replenishment strategy may be a promising approach for skin cancer chemoprevention.
... 42 Fibrillin-1 (FBN1), lysyl oxidase (LOX), and lysyl oxidase-like (LOXL) a key structural component of the elastic fiber network has been shown to decrease in photoaged/aged skin 43,44 and can therefore be considered as new targets to reactivate elastogenesis. Previous studies showed that Vitamin B3 (niacinamide) improves aging facial skin appearance 45 and extends replicative lifespan of human cells. 46 Using in vitro fibroblast culture model, we identified that a complex of niacinamide (active C) and acetyl dipeptide 1 cetyl ester (active D) significantly upregulated the most important dermal genes associated with aging, such as COL1A1, DCN, LOXL, and FBN-1, ( Figure 4A-D). ...
Article
Background: High demand on anti-aging skin care encourage the improvement and development of more personalized formulations with additional benefits for general skin health and age associated skin signs. The skin aging physical and biological phenotypes manifest differently between diverse ethnic populations. A highly polluted environment can be viewed as an extrinsic factor accelerating the skin aging process. Aim: To develop a unique formula with active complexes, having multifunctional effects for anti-pollution, brightening and anti-aging/barrier strengthening purposes with confirmed activities in vitro and ex vivo skin models, suitable for polluted skin. Methods: In vitro culture model with primary human skin cells, ex vivo studies with full-thickness human skin, melanocyte 3D coculture model, gene expression of epidermal and dermal genes, anti-glycation, proteasomal activity, melanin, and cytokine assays. Results: In vitro and ex vivo studies clearly demonstrated that diglucosyl gallic acid (active A) and the formulation complex inhibited pollution mediated MMP1 protein, CYP1A1 gene expression, and IL-6 protein secretion, while caprylic/capric triglyceride, diacetyl boldine (active B) had anti-melanogenic effect in in vitro primary melanocyte monoculture and 3D spheroid model. Another active compound, acetyl dipeptide 1 cetyl ester (active D), significantly upregulated epidermal barrier genes (Aquaporin 3 [AQP3], Filaggrin [FLG], caspase 14, and keratin 10) in human primary keratinocytes. Interestingly, both acetyl dipeptide 1 cetyl ester (active D) and niacinamide (active C) improved dermal gene expression (fibrillin-1, Collagen type 1 alpha 1, Decorin, Lysyl oxidase-like 1) and, moreover, had significant anti-glycant and proteasomal promoter activity in human primary fibroblasts. Conclusion: Considering consumers need in heavily polluted areas, we developed a multipurpose formulation comprised of unique active complexes toward pollution, pollution induced inflammation, skin brightening, and antiaging concerns with beneficial results demonstrated by in vitro and ex vivo studies.
... 46 In one randomized clinical trial, female subjects (n=50) with signs of facial photoaging including fine lines and wrinkles, poor texture, and hyperpigmented spots applied 5% niacinamide to half of the face and its vehicle control to the other half twice daily for 12 weeks. 47 Facial images and instrumental measures were obtained at baseline and at four-week intervals. significant improvements in skin appearance included reduction in fine lines and wrinkles, hyperpigmented spots, red blotchiness, sallowness, and skin elasticity. ...
Article
Full-text available
Mature skin is prone to bruising, resulting in a condition known as actinic purpura, characterized by unsightly ecchymosis and purple patches. Similar to other skin conditions, the incidence of actinic purpura increases with advancing age and occurs with equal frequency among men and women. The unsightly appearance of actinic purpura may be a source of emotional distress among the elderly. A new product has been formulated specifically for the treatment of actinic purpura. This product contains retinol, ahydroxy acids, arnica oil, ceramides, niacinamide, and phytonadione, which effectively treat actinic purpura by improving local circulation, thickening the skin, and repairing the skin barrier. The objective of this paper is to review the beneficial properties of these ingredients and their respective roles in the treatment of actinic purpura.
... More recent studies have noted that topical niacinamide is extremely well tolerated by facial skin that this agent provides several beneficial effects in reducing sebum production. 4,5 The present study was done to compare the efficacy of 5% Benzoyl peroxide gel and 4% Nicotinamide gel in mild to moderate acne of inflammatory origin. ...
Article
Background: Acne vulgaris is a dermatological disorder characterised by formation of comedones and inflammatory lesions. The treatment of acne basically involves reduction of lesions. Benzoyl peroxide, in concentrations of 5%, 10%, and 20%, has been used effectively in the treatment of acne for more than 20 years. Nicotinamide/ Niacinamide is a newly-approved anti-acne drug with a potent anti-inflammatory effect. The present study assessed the efficacy of 5% Benzoyl peroxide gel in comparison to 4% Nicotinamide gel for topical treatment of mild to moderate acne vulgaris.Methods: In this study, the patients with mild to moderate acne vulgaris with inflammation were divided into two groups, group I was treated with topical 5% Benzoyl peroxide gel whereas topical Nicotinamide gel was given to the group II. Assessment of efficacy was done by total lesion counting according acne global severity index, the results were compared at the end of 2 weeks and 4 weeks with the baseline values.Results: At the end of this study, it was found that the reduction of inflammatory and total percentage of decrease in counts of lesions from baseline were highly significant in both the groups (p<0.001), between the groups, differences were statistically significant (p<0.001), therefore 5% Benzoyl peroxide gel has better efficacy than 4% Nicotinamide gel.Conclusions: Benzoyl peroxide is more efficacious than 4 % Nicotinamide gel in mild to moderate acne.
... Efekat gela sa 4% niacinamida u nezi kože sklone aknama je uporediv sa efektima 1% klindamicin gela (46). Ispitivanja su takođe potvrdila da upotreba niacinamida značajno smanjuje fine linije i bore, hiperpigmentacije, kao i da poboljšava elastičnost kože (47,48). ...
Article
Full-text available
Vitamins A, E, C, B3 and provitamin B5 (panthenol), and their numerous derivatives are most widely used in cosmetic products. Cosmetic retinoids (retinol, retinaldehyde, and retinyl esters) have been used for years in cosmetic treatments of (photo)aged skin - brightened hyperpigmentation, reducing roughness of the skin and fine lines and wrinkles. Using the new vitamin A derivative, retinyl retinoate, is considered to overcome the problems associated with instability and undesirable effects of retinol. Hydroxypinacolone retinoate is a new anti-aging ingredient with the efficacy of retinol, but with significantly less irritant potential. Vitamin E (tocopherol) slows down the formation of wrinkles and alleviates the existing ones. Because of the pronounced instability, vitamin E is used in the form of esters, usually as tocopheryl acetate. The novelty on the market is a water-soluble derivative of vitamin E - sodium tocopheryl phosphate. Vitamin C also has positive effects on the skin. However, free vitamin C (ascorbic acid) is very unstable and easily loses its activity. Newer derivatives of vitamin C, which may be water-soluble, amphiphilic or liposoluble, have improved stability compared to the ascorbic acid. They are used in skin care and skin lightening products. Panthenol, which is a very good moisturizer, has been used in various cosmetic products for skin and hair for many years. Vitamin B3 (niacinamide) is commonly used in facial day creams, as skin conditioner. Vitamins in cosmetic products can be considered as safe cosmetic active ingredients, when used in appropriate chemical forms and in allowed concentrations.
... Niacynamide (used in the study product in low concentration) has a delicate lightening effect, improves skin texture and exhibits anti-inflammatory activity [34]. Hence, it constitutes a beneficial addition to cosmetic therapy in AV patients. ...
... Moreover, in vitro and in vivo studies have demonstrated that NA possesses antioxidant properties as well [20,21]. The NA has been incorporated into topical ointments targeted for a wide range of dermatological disorders [22][23][24]. Although there are concerns regarding the worldwide increase of the gelatinous biomass of jellyfish, an increasing number of results also showed that the jellyfish could be used as a new source of marine drugs [25,26]. ...
Article
Full-text available
Nicotinamide (NA), a water-soluble vitamin B3, has been shown to exert cellular-protective effects against reactive oxygen species (ROS). In order to improve the cellular-protective effects of NA, we synthesized a novel compound, nicotinyl–isoleucine–valine–histidine (NA–IVH), by combining NA with jellyfish peptides’ IVH. In the present study, we examined the cellular-protective effects of the novel synthetic nicotinyl-peptide, NA–IVH. We found that NA–IVH enhances the radical scavenging activity with a robust increase of the nuclear factor (erythroid-derived 2)-like factor (Nrf2) expression in human HaCaT keratinocytes. In addition, NA–IVH protected the cells from hydrogen peroxide (H2O2)-induced cell death. Interestingly, NA–IVH exhibited an improved wound-healing effect in a high glucose condition, possibly through the regulation of reactive oxygen species (ROS). Collectively, our results imply that a novel nicotinyl-peptide, NA–IVH, has a wound-healing effect in a hyperglycemic condition, possibly by modulating excessive ROS.
... Urea, one of the most widely used cosmetic actives, showed an enhancement of barrier function by inducing epidermal differentiation, increasing lipid content and increasing antimicrobial peptide expression (Grether-Beck et al., 2012) Another specific activity of the PUFA in epidermis is the activation of the TLR2 (co-localized in the lipid rafts of the cellular membrane) receptor pathway that induces the polarization of macrophages into the inflammation-driving M1 phenotype and contributes to immune defense via the synthesis and release of pro-inflammatory cytokines (Hellwing et al., 2018), Alternatively, a B vitamin, niacinamide, has been shown to increase the epidermal production of skin barrier lipids, (ceramides), and proteins (keratin, involucrin, and fillagrin) (Bissett et al., 2005) In other studies, the anti-ageing effect of an aqueous extract of Gromwell (Lithospermum erythrorhizon) was associated (Kim et al., 2012) with the increase in both lipids markers for phopholipids and glucosylceramides in aged fibroblasts. ...
Article
Full-text available
Skin is a representative model of the complex metabolism that lipids may trigger. It is known that the biosynthesis of these lipids in mammalian cells generally ensures the cell membranes stability and participates to the signaling function. In the inner layers of the skin, the “de-novo” synthesis is the driving force ensuring proliferation, development and intercellular signaling. To promote stratum corneum formation, lipid catabolism leads to the renewal of ceramides, fatty acids and cholesterol that are responsible for the cohesion of the stratum corneum, its permeability, hydration, moisturization and signalling with the outer skin layers, appendages and inner layers secretion (cytokines, neuropeptides). Some actives applied in local treatments (i.e., peptides, n-3 polyunsaturated fatty acids (PUFA), ceramides, urea or an aqueous extract of Gromwell) and in oral treatment (i.e., sphingomyelin, n-3 polyunsaturated fatty acids (PUFA)) promote sphingosine 1-phosphate (S1P) production by the sphingolipid rheostat via triggering the salvage process along with autophagy and detoxification in aged skin. This review gives some basis for using the concept of sphingolipid metabolism rheostat in skin as the driving force for the development of new cosmetic actives ingredients or for repositioning the benefits of other actives for the skin.
... Studies have revealed significant reduction in fine lines and wrinkles, hyper-pigmented spots, red blotchiness and skin swelling, as well as improved skin elasticity. [5,6] d)N-acetyl-glucosamine (NAG). NAG is a more stable form of glucosamine, and may prevent new signs of photo-damage from occurring, and fade existing imperfections by interrupting the chemical signals that promote melanin production. ...
... Nicotinamide (NAM), also known as niacinamide or vitamin B-3, is a nicotinamide adenine dinucleotide (NAD þ ) precursor that is rapidly incorporated into the NAD(H)/NADP(H) pool. NAM has beneficial effects on skin appearance, such as reducing melasma (Navarrete-Solis et al., 2011), sallowness, hyperpigmentation, and wrinkles (Bissett et al., 2004(Bissett et al., , 2005. It has thus been classified as an anti-aging molecule. ...
Article
Nicotinamide (NAM) is the main precursor of nicotinamide adenine dinucleotide (NAD ⁺ ), a coenzyme essential for DNA repair, glycolysis, and oxidative phosphorylation. NAM has anti-aging activity on human skin, but the underlying mechanisms of action are unclear. Using 3-dimensional organotypic skin models, we show that NAM inhibits differentiation of the upper epidermal layers and maintains proliferation in the basal layer. In 2-dimensional culture, NAM reduces the expression of early and late epidermal differentiation markers and increases the proliferative capacity of human primary keratinocytes. This effect is characterized by elevated clonogenicity and an increased proportion of human primary keratinocyte stem cell (holoclones) compared to controls. By contrast, preventing the conversion of NAM to NAD ⁺ using FK866 leads to premature human primary keratinocyte differentiation and senescence, together with a dramatic drop in glycolysis and cellular adenosine triphosphate levels while oxidative phosphorylation is moderately affected. All these effects are rescued by addition of NAM, known to compete with FK866, which suggests that conversion to NAD ⁺ is part of the mechanistic response. These data provide insights into the control of differentiation, proliferation, and senescence by NAM and NAD ⁺ in skin. They may lead to new therapeutic advances for skin conditions characterized by dysregulated epidermal homeostasis and premature skin aging, such as photoaging.
... Nicotinamide has been shown to be beneficial in treating melasma 17 and hyperpigmentation, 18 and in abrogating features of ageing, with trials reporting a reduction in objective indices, which included wrinkles, lentigines and improvement in elasticity, following topical nicotominade application, 19,20 The ability of nicotinamide to improve melasma and hyperpigmentation is postulated to be secondary to reduced melanosome transfer within both melanocytes and keratinocytes. 21 A pilot study found that a metabolite of nicotinamide (1-methylnicotinamide) 0.25% applied topically twice daily for 4 weeks showed an observed improvement in rosacea in 26/34 patients. ...
Article
Full-text available
Nicotinamide (niacinamide) is the water-soluble, amide form of vitamin B3. We review the evidence underlying the use of nicotinamide for various dermatological indications, including nonmelanoma cancer prophylaxis, blistering disorders, acne vulgaris and cosmetic indications, and speculate upon its future role in dermatological practice.
... Topical nicotinamide (niacinamide, vitamin B3) improves skin appearance and provides beneficial effects in prevention of the loss of dermal collagen that characterizes photoaging [147][148][149]. Vitamin B 3 , a precursor of Nicotinamide Adenine Dinucleotide (NAD), can also prevent UV-induced depletion of ATP in keratinocytes, leading to the acceleration of energy-dependent DNA repair processes [150]. ...
Article
Full-text available
Skin aging is accompanied by a gradual loss of function, physiological integrity and the ability to cope with internal and external stressors. This is secondary to a combination of complex biological processes influenced by constitutive and environmental factors or by local and systemic pathologies. Skin aging and its phenotypic presentation are dependent on constitutive (genetic) and systemic factors. It can be accelerated by environmental stressors, such as ultraviolet radiation, pollutants and microbial insults. The skin's functions and its abilities to cope with external stressors are regulated by the cutaneous neuroendocrine systems encompassing the regulated and coordinated production of neuropeptides, neurohormones, neurotransmitters and hormones, including steroids and secosteroids. These will induce/stimulate downstream signaling through activation of corresponding receptors. These pathways and corresponding coordinated responses to the stressors decay with age or undergo pathological malfunctions. This affects the overall skin phenotype and epidermal, dermal, hypodermal and adnexal functions. We propose that skin aging can be attenuated or its phenotypic presentation reversed by the topical use of selected factors with local neurohormonal activities targeting specific receptors or enzymes. Some of our favorite factors include melatonin and its metabolites, noncalcemic secosteroids and lumisterol derivatives, because of their low toxicity and their desirable local phenotypic effects.
... In addition, skin yellowing (sallowness) versus control was significantly improved [159]. In addition to previously observed benefits for topical niacinamide, additional effects were identified by Bissett et.al, 2005, which was improved appearance of skin wrinkles and yellowing and improved elasticity [160]. ...
Article
Hyperpigmentation is one of the most common skin disorders that affects both men and women of all ethnic groups, caused by several factors, such as UV exposure and skin inflammation. Topical whitening agents were found to be the best and the least aggressive therapy for treating hyperpigmentation compared to instrumental approaches. However, topical treatment faces several obstacles due to the low stability of the whitening agents. The number of patients that visit dermatologists with pigmentary disorders is significant. Patients are often overwhelmed with numerous OTC skin lightening agents, many without clinical evidence of efficacy. However, evidence-based studies on many of these agents are still lacking. The treatment of melasma should include a multimodality approach that incorporates photoprotective agents, antioxidant treatments, skin lighteners, exfoliants, and resurfacing procedures, as needed. Evidence-based studies suggest that first line therapies for melasma encompass intense photoprotection and topical lightening agents. Second-line treatments, such as chemical peels and lasers, are efficacious in some patients, but these approaches can be associated with acute and long-term complications, particularly in individuals with darker skin types. Given the global negative impact of melasma on the quality of life, a quest to find more efficacious treatments that offer sustained long-term remission for patients with this frustrating and therapeutically challenging disorder is ongoing.
... In fact, most clinical studies relate the performance of anti-ageing products as compared to baseline and untreated skin. Yet few active compounds have been tested in vehicle-controlled studies, that is retinoids [4-8, 25, 35, 36, 40], niacinamide [37,38], kinetin in combination with niacinamide [39], tetra-hydro-jasmonic acid [26,40], 1-carbamimidoyl-L-proline [41], ascorbic acid [42] and hyaluronic acid [43]. Peptides are commonly used in anti-ageing creams but clinical evidence remains largely unpublished, with some exceptions (reviewed in [44]). ...
Article
Objective: Acetyl aspartic acid (A-A-A) was discovered through gene array analysis with corresponding Cmap analysis. We found that A-A-A increased keratinocyte regeneration, inhibited dermal matrix metalloprotease (MMP) expression and relieved fibroblast stiffness through reduction of the fibroblast stiffness marker F-actin. Dermal absorption studies showed successful delivery to both the epidermal and dermal regions, and in-use trial demonstrated that 1% A-A-A was well tolerated. In this study, the aim was to investigate whether A-A-A could stimulate the synthesis of extracellular matrix supporting proteins in vivo and thereby improving the viscoelastic properties of human skin by conducting a dual histological and biophysical clinical study. Method: Two separate double-blind vehicle-controlled in vivo studies were conducted using a 1% A-A-A containing oil-in-water (o/w) emulsion. In the histological study, 16 female volunteers (>55 years of age) exhibiting photodamaged skin on their forearm were included, investigating the effect of a 12-day treatment of A-A-A on collagen IV (COLIV) and fibrillin-1. In a subsequent pilot study, 0.1% retinol was used for comparison to A-A-A (1%). The biomechanical properties of the skin were assessed in a panel of 16 women (>45 years of age) using the standard Cutometer MPA580 after topical application of the test products for 28 days. The use of multiple suction enabled the assessment of F4, an area parameter specifically representing skin firmness. Results: Twelve-day topical application of 1% A-A-A significantly increased COLIV and fibrillin with 13% and 6%, respectively, compared to vehicle. 1% A-A-A and 0.1% retinol were found to significantly reduce F4 after 28 days of treatment by 15.8% and 14.7%, respectively, in the pilot Cutometer study. No significant difference was found between retinol and A-A-A. However, only A-A-A exhibited a significant effect vs. vehicle on skin firmness which indicated the incremental benefit of A-A-A as a skin-firming active ingredient. Conclusion: In this study, we showed the in vivo efficacy of 1% A-A-A both on a protein level (fibrillin and collagen IV) and on a clinical end point, specifically skin firmness, providing proof that, acetyl aspartic acid has a strong potential as an anti-ageing 'cosmeceutical' ingredient answering the needs of our key consumer base.
... The present paper introduces a Monte Carlo approach that can be combined with toxicity characterization models to specify substance input data as variable distributions, and presents resulting CFs as frequency distributions. To illustrate this sensitivity-based approach, we apply it to USEtox 1.01 to develop stochastic aquatic ecotoxicity CFs for the vitamin B derivative niacinamide (CAS 98-92-0), currently used at low concentrations in commercial personal care products because of its antioxidant properties (Bissett et al. 2006). This illustration represents a hypothetical case in which personal care product developers are unsure about the potential ecotoxicity impacts and want to improve their confidence. ...
Article
Full-text available
Purpose Product developers using life cycle toxicity characterization models to understand the potential impacts of chemical emissions face serious challenges related to large data demands and high input data uncertainty. This motivates greater focus on model sensitivity toward input parameter variability to guide research efforts in data refinement and design of experiments for existing and emerging chemicals alike. This study presents a sensitivity-based approach for estimating toxicity characterization factors given high input data uncertainty and using the results to prioritize data collection according to parameter influence on characterization factors (CFs). Proof of concept is illustrated with the UNEP-SETAC scientific consensus model USEtox. Methods Using Monte Carlo analysis, we demonstrate a sensitivity-based approach to prioritize data collection with an illustrative example of aquatic ecotoxicity CFs for the vitamin B derivative niacinamide, which is an antioxidant used in personal care products. We calculate CFs via 10,000 iterations assuming plus-or-minus one order of magnitude variability in fate and exposure-relevant data inputs, while uncertainty in effect factor data is modeled as a central t distribution. Spearman’s rank correlation indices are used for all variable inputs to identify parameters with the largest influence on CFs. Results and discussion For emissions to freshwater, the niacinamide CF is near log-normally distributed with a geometric mean of 0.02 and geometric standard deviation of 8.5 PAF m³ day/kg. Results of Spearman’s rank correlation show that degradation rates in air, water, and soil are the most influential parameters in calculating CFs, thus benefiting the most from future data refinement and experimental research. Kow, sediment degradation rate, and vapor pressure were the least influential parameters on CF results. These results may be very different for other, e.g., more lipophilic chemicals, where Kow is known to drive many fate and exposure aspects in multimedia modeling. Furthermore, non-linearity between input parameters and CF results prevents transferring sensitivity conclusions from one chemical to another. Conclusions A sensitivity-based approach for data refinement and research prioritization can provide guidance to database managers, life cycle assessment practitioners, and experimentalists to concentrate efforts on the few parameters that are most influential on toxicity characterization model results. Researchers can conserve resources and address parameter uncertainty by applying this approach when developing new or refining existing CFs for the inventory items that contribute most to toxicity impacts.
... At present, there is no clear evidence that topical application of DNA repair enzymes or nicotinamide, which is highly effective in preventing actinic keratosis, have benefits in reducing the incidence of chronic sun exposure-related photoaging. [65][66][67] ...
Article
Full-text available
Background: Extrinsic skin aging or photoaging was previously thought to be almost exclusively due to solar ultraviolet (UV) radiation. However, recent literature has described other contributing factors and clarification is thus required as to what extent and what type of daily photoprotection is needed to mitigate extrinsic skin aging. Methods: We reviewed the existing scientific evidence on daily photoprotection, and specific requirements at the product level, to prevent extrinsic skin aging. We critically reviewed the existing evidence on potential ecological and toxicological risks which might be associated with daily photoprotection. Results: Evidence shows that broad protection against the entire solar range of UVB, UVA, UVA1, visible light and short infrared (IRA) is required to prevent extrinsic aging. Other exposomal factors, such as air pollution and smoking, also contribute to skin aging. Daily broad-spectrum sunscreen photoprotection should thus contain antioxidant ingredients for additional benefits against UV, IRA and pollution-induced oxidative stress as well as anti-aging active ingredients to provide clinical benefits against skin aging signs, such as wrinkles and dark spots. Broad-spectrum sunscreen containing pigments, such as iron oxide, may be required for melasma prevention. There is no conclusive clinical evidence that daily sunscreen use is unsafe or that it compromises vitamin D synthesis. Conclusion: Daily use of broad-spectrum sunscreen containing antioxidant and anti-aging active ingredients can effectively reduce extrinsic aging.
... Skin elasticity is improved by niacinamide used in MNF that inhibits the dermal matrix glycation and increased concentration of collagen (dermal remodeling) [39]. Niacinamide and ferulic acid both increase the level of NADP which is also involved in the increased production of collagen [6,17]. ...
Article
Full-text available
Objective: Multiple emulsions have the ability to incorporate both lipophilic and hydrophilic actives in the same preparation and facilitate permeation of active ingredients through skin. The current study was aimed at formulating niacinamide/ferulic acid-loaded stable multiple emulsion (MNF) and its in vitro/in vivo characterization as a cosmeceutical product. Methods: Both the compounds were evaluated for their radical scavenging potential by the DPPH method and FTIR analysis. Then, placebo and active formulations were prepared using a double emulsification method and were investigated for stability testing (changes in color, odor, and liquefaction on centrifugation, pH, and globule size) for a period of three months. Afterwards, MNF was investigated for in vitro sun protection factor, rheological studies, entrapment efficiency, zeta potential, zeta size, and ex vivo permeation. Moreover, after ensuring the hypoallergenicity and safety, it was also checked for its cosmeceutical effects on human skin using noninvasive biophysical probes in comparison with placebo. Results: Results demonstrated that MNF showed a non-Newtonian behavior rheologically and both MNF and placebo were stable at different storage conditions. Entrapment efficiency, zeta potential, and zeta size were 93.3%, -5.88 mV, and 0.173 μm, respectively. Moreover, melanin, sebum, and skin erythema were significantly reduced while skin elasticity and hydration were improved. Conclusion: It is evident that niacinamide and ferulic acid can be successfully incorporated in a stable multiple emulsion which has potent cosmeceutical effects on human skin.
... A total of 49 women completed the study with all subjects using vehicle on one side of their face, and for the other side, 31 of the subjects used 1% SFC gel; the remaining 18 subjects used 5% niacinamide as a comparator, as it has been previously shown to improve facial skin appearance [28]. Results of the clinical grading of wrinkles on the crow's feet area shows statistically significant improvement from baseline and vehicle at weeks 8 and 12 for 1% SFC gel, while 5% niacinamide only exhibits significant improvement at week 12 (Figure 3). ...
Article
Full-text available
Over the past 15 years, small molecule isoprenylcysteine (IPC) analogs have been identified as a potential new class of topical anti-inflammatories. Clinical studies have demonstrated that IPCs are both safe and effective in promoting healthy skin when applied topically. This work aims to demonstrate N-Succinyl-S-farnesyl-L-cysteine (SFC) as a novel IPC molecule that provides a broad spectrum of benefits for skin. Human promyelocytic cell line HL-60, human dermal microvascular endothelial cells (HDMECs), human dermal fibroblasts (HDFs), and normal human epidermal keratinocytes (NHEKs) were exposed in culture to various inducers to trigger reactive oxygen species, cytokines, or collagenase production. A 49-subject randomized double-blind, vehicle-controlled, split face trial was performed with 1% SFC gel, or 5% niacinamide and vehicle applied for 12 weeks to evaluate anti-wrinkle and anti-aging endpoints. We demonstrated that SFC inhibited GPCR and TLR-induced pro-inflammatory cytokine release in NHEKs and HDMECs from several inflammatory inducers such as UVB, chemicals, cathelicidin, and bacteria. SFC successfully reduced GPCR-induced oxidation in differentiated neutrophils. Moreover, photoaging studies showed that SFC reduced UVA-induced collagenase (pro-MMP-1) production in HDFs. Clinical assessment of 1% SFC gel demonstrated improvement above the vehicle for wrinkle reduction, hydration, texture, and overall appearance of skin. N-Succinyl-S-farnesyl-L-cysteine (SFC) is a novel anti-inflammatory small molecule and is the first farnesyl-cysteine IPC shown to clinically improve appearance and signs of aging, while also having the potential to ameliorate inflammatory skin disorders.
... All of these effects can help reverse some of the signs of skin aging. For this purpose, the vitamin is used in cosmeceutical products in concentrations from 3.5% to 5% [87,88]. In 2005, the CIR Expert Panel stated that niacinamide and niacin are safe in the and concentration (0.0001-3%) in cosmetic products [89]. ...
Article
Full-text available
The average woman uses 12 different cosmetic products every day, but they can have a negative effect on human health. Therefore, in recent years, consumer preferences have changed towards buying natural or ecological cosmetics free from preservatives or unnecessary dyes. The aim of this work is to discuss the use of dyes, minerals, and vitamins in cosmetics in terms of their safety and impact on human health. These substances are very important in the cosmetics industry. Most of them are of natural origin. Some minerals used in the production of face masks or creams are recommended to work against inflammations such as ulcers and acne. Clay minerals have exceptional qualities, among others, low or no toxicity and high bio-compatibility. However, some of them may be harmful. For example, the safety of using talc has been widely debated in recent years. Cosmetic-grade talc cannot contain detectable fibrous asbestos minerals. Moreover, talc should not be applied to the skin when the epidermal barrier is missing or significantly disrupted. The use of talc in cosmetic products in the European Union is restricted. Vitamins are one of the most commonly used, biologically active, and easily accessible components in cosmetics. For example, provitamin B5 (D-panthenol) is a bioactive substance. In cosmetic preparations, it has a softening, repairing, and anti-inflammatory effect and is responsible for regulating sebum secretion. However, some vitamins may be harmful to human health. For example, the use of skin-whitening cosmetics containing vitamin C causes allergic contact dermatitis, whereas the most common adverse effect of topical use of vitamin A is skin irritation, erythema, and peeling. Dyes, which are used to color cosmetics, do not improve the condition of the skin, hair, or nails. Some of them may be harmful to human health. For example, the dye CI 60730 (Acid Violet 43) is prohibited for use in eye products and cosmetics that have contact with mucous membranes. In conclusion, some of the popular cosmetic ingredients discussed in this paper may exert a negative influence on human health, and many of these harmful effects have been discovered recently. Therefore, there is a need for further studies on the possible negative effects of dyes, minerals, and vitamins used in cosmetic products.
... Nicotinamide (NAM), i.e., niacinamide or vitamin B3, is a NAD + precursor with antiaging properties (Bissett et al., 2004;Bissett et al., 2005;Oblong, 2014). We previously showed that NAM promotes human keratinocyte stem cell maintenance, which may contribute to its beneficial effect on "chronological" aging (Tan et al., 2019). ...
Article
Full-text available
Nicotinamide (NAM), a NAD⁺ precursor, is known for its benefits to skin health. Under standard culture conditions, NAM delays the differentiation and enhances the proliferation of human primary keratinocytes (HPKs), leading to the maintenance of stem cells. Here, we investigated the effects of NAM on photoaging in 2D HPK cultures and 3D organotypic epidermal models. In both models, we found that UVB irradiation and hydrogen peroxide induced HPK premature terminal differentiation and senescence. In 3D organotypics, the phenotype was characterized by a thickening of the granular layer expressing filaggrin and loricrin, but thinning of the epidermis overall. NAM limited premature differentiation and ameliorated senescence, as evidenced by the maintenance of lamin B1 levels in both models, with decreased lipofuscin staining and reduced IL-6/IL-8 secretion in 3D models, compared to UVB-only controls. In addition, DNA damage observed after irradiation was accompanied by a decline in energy metabolism, while both effects were partially prevented by NAM. Our data thus highlight the protective effects of NAM against photoaging and oxidative stress in the human epidermis, and pinpoint DNA repair and energy metabolism as crucial underlying mechanisms.
... It is widely used in cosmetics including skin and hair care products. 25 Niacinamide has long been used as an active ingredient in anti-hair loss preparations. There are few studies, however, on the efficacy and underlying mechanisms of niacinamide for anti-hair loss, have been reported. ...
Article
Full-text available
Purpose: An increasing number of people are suffering from hair loss disorders. Niacinamide has long been used as an active ingredient for anti-hair loss preparations but the exact mechanism has not been clearly elucidated yet. The effects of niacinamide were investigated in cultured human dermal papilla cells (hDPCs). Methods: To investigate the anti-hair loss effect of niacinamide and its molecular mechanisms, Western blot analysis, ELISA, quantitative RT-PCR and immunocytochemistry were performed. To study the protective effects of niacinamide against H2O2-induced oxidative stress, ROS generation and cytotoxicity were evaluated by DCF-DA assay and LDH release assay, respectively. Minoxidil was used as a positive control. Results: Niacinamide decreased the protein expression level of DKK-1 which promotes regression of hair follicles by inducing catagen. The protein expression levels of cell senescence markers, p21 (CDKN1A) and p16 (CDKN2A) which are related to cell cycle arrest, were decreased. The expression of versican was increased by niacinamide treatment in cultured hDPCs. We have found that niacinamide decreased the H2O2-induced intracellular ROS production in cultured hDPCs. Moreover, niacinamide decreased the protein expression levels of H2O2-induced p21 and p16 and diminished the secretion of H2O2-induced DKK-1. Conclusion: Our data demonstrate that niacinamide could enhance hair growth by preventing oxidative stress-induced cell senescence and premature catagen entry of hair follicles.
... Therefore, it could be concluded that phenolics were major compounds responsible for the antioxidant properties of C. carandas extracts. Since research has proposed that topical antioxidants be used for the treatment of skin aging [44][45][46], C. carandas extracts, especially EL, have been suggested to be used as natural antioxidants, which could prevent skin aging. A previous study reported that antioxidants play an important role in the prevention and treatment of UV-induced skin aging due to the reduction in oxidized proteins, which strongly correlates with the severity of photo-aging clinical characteristics [47]. ...
Article
Full-text available
In this study, the potential of Carissa carandas Linn. as a natural anti-aging, antioxidant, and skin whitening agent was studied. Various parts of C. carandas, including fruit, leaf, seed, and pulp were sequentially extracted by maceration using n-hexane, ethyl acetate, and ethanol, respectively. High-performance liquid chromatography, Folin–Ciocalteu, and Dowd method were used to investigate their chemical compositions. The inhibitory activities of oxidation process, matrix metalloproteinases (MMPs), elastase, hyaluronidase, and tyrosinase were analyzed. Cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide assay in a human epidermal keratinocyte line (HaCaT). The results exhibited that ethyl acetate could extract the most ursolic acid from C. carandas, while ethanol could extract the most phenolics and flavonoids. The leaf extract had the highest content of ursolic acid, phenolics, and flavonoids. The leaf extracted with ethyl acetate (AL) had the highest ursolic acid content (411.8 mg/g extract) and inhibited MMP-1, NF-kappa B, and tyrosinase activity the most. Ursolic acid has been proposed as a key component in these biological activities. Although several C. carandas extracts are beneficial to human skin, AL has been proposed for use in cosmetics and cosmeceuticals due to its superior anti-wrinkle, anti-inflammation, and whitening properties.
... For example, wrinkly dogs like Shar Peis have mucinosis -with high hyaluronic acid levels in both cutaneous tissues and the blood stream-due to an excess in the activity (overexpression) of the HAS2 enzyme that produces more hyaluronic acid [11]. Niacinamide in topical preparations has been shown to cause an improved appearance of skin wrinkles, reducing yellowing and improving skin elasticity [12]. Tocopherol (vitamin E), when applied topically to skin has been shown to reduce erythema after sunburn, chronic UVB-induced skin damage, and carcinogenesis in several published studies [13,14]. ...
Article
Full-text available
Objective: The primary aim of this study was to evaluate the performance of a commercially manufactured study product-a non-toxin-based topical skin serum-in terms of its wrinkle reducing capability in women concerned about the appearance of their wrinkles.
... Additionally, a niacinamidecontaining moisturizer applied with tretinoin therapy enhanced the response to tretinoin, improved the stratum corneum, and decreased tretinoin-associated side-effects [62]. Niacinamide is well tolerated by the skin and provided significant improvements versus control in fine lines/wrinkles, hyperpigmentation spots, texture, red blotchiness, elasticity, and skin yellowing versus an oil in water moisturizer control [63,64]. Both niacinamide and 18-β glycyrrhetinic acid are optimal anti-inflammatory molecules for optimizing repair of the compromised skin barrier. ...
... Surjana excision repair and enhances repair of UVB radiationinduced cyclobutane pyrimidine dimers and UVA radiation-induced 8-oxo-7,8-dihydro-2′-deoxyguanosine. Multiple randomized, placebo-controlled trials have shown clinical improvement in skin texture, elasticity, and wrinkles after 12 weeks of daily application of cream containing 5% niacinamide [24][25][26]. However, clinical trials with more participants need to be conducted to determine its applicability as a definitive treatment for photoaging. ...
Article
Over-the-counter antiaging formulations aim to prevent or minimize the signs of aging skin, and to maintain the benefits obtained from different cosmetic procedures. Even though a huge selection of such products is available on the market, evidence and good clinical practice of the data supporting their use are oftentimes lacking. In this systematic review, the authors reviewed scientific data available in the published literature on the most common ingredients used in antiaging cosmetics, with a particular focus on in vivo studies.
Chapter
The Food, Drug, and Cosmetic Act defines drugs as products that cure, treat, mitigate or prevent disease, or affect the structure or function of the human body [1]. The dermatology and cosmetic industries recognize “cosmeceuticals” as cosmetics that have drug-like benefits. The term “cosmeceutical” was first used by Dr. Albert Kligman to describe a cosmetic product that exerts a therapeutic benefit in the appearance of the skin, but not necessarily a biologic effect on skin function, which would then classify it as a drug [2–4]. The Food and Drug Administration does not recognize or regulate cosmeceuticals. The symbiotic relationship between a drug and a cosmetic has become increasingly evident with the rapid growth of the cosmeceutical industry over the last decade. There are now both prescription cosmeceuticals and over-the-counter cosmeceuticals available to consumers. This arbitrary distinction varies in different countries. For example, drugs such as tretinoin, available only by prescription in the United States, are sold as over-the-counter cosmeceuticals in Central America. Antiperspirant is also regulated as a drug in the United States while being considered a cosmetic in Europe.
Chapter
Skin aging is the result of two distinct, biological processes which may occur concurrently: extrinsic aging and intrinsic aging. Extrinsic aging of the skin is exemplified by deep, coarse wrinkles, mottled hyperpigmentation and a marked loss of elasticity and recoil. On the other hand, intrinsically aged skin is a slow process which causes changes in tissue structure and impairs function in the absence of additional chemical, biological and physical factors. Our skin provides a very efficient delivery system for chemicals to enter the body. Unfortunately our skin also absorbs toxic chemicals commonly found in personal care products. Consequently, we should switch to natural skin care products. There has been a very long history in human civilization of the usage of natural products; such as herbs, roots, essential oils and flowers for skin care. A cosmetic formulation including natural products can protect the skin against exogenous or endogenous harmful agents, and help to remedy many skin conditions. Although there are several treatments available for aged skin, oral administration supplements and topical application formulations remain the best approach and should be encouraged to all patients. This chapter focuses on the anti-skin aging effects of natural products, such as polyphenols and terpenes using topical application and oral administration. Future prospective for this field of research will focus on natural products combined with molecular techniques; it will help to maximize the desired anti-skin aging benefits.
Chapter
Melasma may be an elusive dyschromia to treat, but science has created a variety of options to choose from. What is imperative is to establish the diagnosis, explore the possible causes to this diagnosis, and educate the patient on her condition. Expectations must be set to ensure cooperation of the patient. A 5-point strategy to the management is offered to optimize success in therapy: continuous protection from the sun, avoidance of factors that may increase melanocyte activity, topical therapies to inhibit melanin synthesis, and procedural means to remove melanin or disrupt melanin granules. Although topical sunscreens and depigmenting agents remain the most important part of treatment, chemical peeling can be offered as a means to hasten lightening of the pigmentation. Utmost consideration to the skin phototype is critical, to avoid aggravating the hyperpigmentation.
Chapter
Full-text available
The skin is the primary protection of the body against external injuries and is essential in the maintenance of general homeostasis. The dermis, located beneath the epidermis, represents the thickest compartment of the skin and is mainly composed of a dense collagen network supporting specific dermal apparatus such as hair follicles, sebaceous and sweat glands. Dermal (myo)fibroblasts play a major role in the synthesis and maintenance of the extracellular matrix (ECM) as well as in the wound healing process. During aging, the dermal ECM and associated resident cells undergo senescence affecting both the structure of the dermis and its role in skin repair. In addition, extrinsic factors such as ultraviolet (UV) irradiation and intrinsic factors such as diabetes or medicines can further accelerate this phenomenon. Thus, aging has direct consequences on the dermis via both the alteration of ECM components and the impairment of (myo)fibroblast function.
Article
In summary, multiple studies have documented the efficacy of topical agents (retinoids, antioxidants, and topical bleaching agents) used in combination with superficial and/or mediumdepth or deep peeling agents for photodamage. The treatment of photodamage requires a multifaceted approach incorporating sun protection, antioxidants, exfoliating agents, retinoids, and resurfacing procedures. Despite the evolution of new and advanced laser technologies, chemical peeling remains a viable, efficacious, and cost-effective treatment for photodamage.
Article
There is a growing demand for noninvasive anti-aging products for which the periorbital region serves as a critical aspect of facial rejuvenation. This article reviews a multitude of cosmeceutical ingredients that have good scientific data, specifically for the periorbital region. Topical treatment options have exponentially grown from extensively studied retinoids, to recently developed technology, such as growth factors and peptides. With a focus on the periorbital anatomy, the authors review the mechanisms of action of topical cosmeceutical ingredients, effectiveness of ingredient penetration through the stratum corneum, and validity of clinical trials.
Chapter
Die Haut als Ich-bezogenes Organ des menschlichen Körpers dient auch der Kommunikation mit dem Gegenüber und wurde seit jeher bewusst in ihrer Erscheinung modifiziert. So reichen die Ursprünge kosmetischer Behandlungen durch Externa (auch zur Faltenbehandlung) viele Jahrtausende zurück. Schon im alten Ägypten spielten kosmetische Anwendungen, nicht nur bei Frauen, sondern auch bei Männern, eine große Rolle.
Chapter
The term “cosmeceuticals”, suggested by Kligman more than 20 years ago, refers to topical products that lie in a gray zone where they are viewed as having both pharmaceutical and cosmetic properties [1]. Although the neologism was innovative and relevant, it was rejected from the US Food, Drug, and Cosmetic Act that, according to the 1938s US Congress, labels as drug every substance for use in the diagnosis, cure, treatment or prevention of disease, and as cosmetic any product intended for beautifying and promoting attractiveness. In spite of this, the term cosmeceuticals has recently been gaining increasing popularity, as the term cosmetic seems to be restrictive for those substances that have druglike beneficial effects. On the other hand, the “cosmeceuticals” concept has caused a lot of confusion, because of similar neologisms such as neutraceuticals and/or neoceuticals. Actually, in USA and Canada, most cosmeceuticals are regulated as over the counter (OTC) products, while in Europe they are considered as cosmetics. Only in Japan, a new class of products, called quasi-drugs, has been created [2].
Chapter
During the recent decades, dermal delivery has achieved visible popularity mainly due to the increase of chronic skin diseases and the demand for targeted delivery and patient compliance. Dermal delivery provides an attractive alternative to oral drug delivery, promoting the drug application directly at the site of action, resulting in higher localized drug concentration with reduced systemic drug exposure. Among several types of drug delivery systems used in dermal delivery are the lipid nanoparticles, which include solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). These lipid nanocarriers have attracted great interest and have been intensively studied for their use in dermal applications. Lipid nanoparticles increase the transport of active compounds through the skin by improving drug solubilization in the formulation, drug partitioning into the skin, and fluidizing skin lipids. Moreover, these nanocarriers are composed of biologically active and biodegradable lipids that show less toxicity and offer many favorable attributes such as adhesiveness, occlusion, skin hydration, lubrication, smoothness, skin penetration enhancement, modified release, improvement of formulation appearance providing a whitening effect, and offering protection of actives against degradation.This chapter focuses on the effects of lipid nanoparticles in dermal delivery, on the types of active compounds that are used in their formulation and application, some aspects related to their possible toxicity, and a description of the most commonly used techniques for the evaluation of drug absorption on the skin.
Chapter
Cosmeceuticals have biologically active ingredients and show beneficial results. However, they may not be US FDA approved. Most cosmeceuticals are made of extracts from marine algae, fruits, herbs, and other botanicals, and these ingredients may be existing already. There are a number of topical antiaging cos‐meceuticals that patients can use depending on their needs. Also known as fruit acids, alpha‐hydroxy acids (AHAs) are a group of chemical compounds that consist of a carboxylic acid substituted with a hydroxyl group on the adjacent carbon. The cosmetic and the pharmaceutical market is flooded with lightening products each claiming to be the best, but with limited clinical evidence to support their claim. Botanicals are active compounds that are isolated from plants. The potential concerns could be the lack of proper testing for efficacy. There are many false claims made, and products are highly priced.
Article
Falten reduzieren, die Haut straff halten und einen frischen Teint herbeizaubern — diese Versprechungen machen viele Cosmeceuticals. Sie enthalten meist effektivere Inhaltsstoffe als herkömmliche Kosmetika. Besonders Produkte, die einer vorzeitigen Hautalterung entgegenwirken, sind im Trend. Die Wirksamkeit ist zwar oft wissenschaftlich belegt; allerdings gibt es bei der Anwendung einige Risiken, die Dermatologen und Kosmetiker nicht außer Acht lassen sollten.
Article
The skin age is accompanied by elasticity decrease which results in flaccidity, fine and deep wrinkles besides dehydration. This process can be accompanied by a gradual decrease in melanocytes number associated by an irregular increase of melanogenesis activity which results in discromias disorder as hypo or hyperpigmentation. The interest in new substances with skin rejuvenation properties, especially from natural sources, has increased in the last years. In this way, resveratrol (3,4’,5-trihydroxy-trans-stilbene) is a natural substance and has been increasingly in the cosmetic industry because of its antioxidant, anti-inflammatory and despigmenting properties. The aim of this systematic review was to analyze the potential of resveratrol in promoting skin rejuvenation. Medline and Embase were searched for studies that tested topical formulation with resveratrol in humans and measured the efficacy in skin rejuvenation. Two studies fulfilled the criteria of inclusion. In both studies the authors observed improvement in the global appearance accompanied by improvement in fine lines, shine, firmless, redness and pigmentation. Despite both studies showed the benefits of topical resveratrol, none of them used the substance alone.
Thesis
This thesis addresses the development of topical formulations designed to treat atopic dermatitis (AD) using nicotinamide (NA). A rational approach to the development of topical formulations based on the physical and chemical properties of the drug and vehicle components is studied. This approach is an alternative to the model of formulation development where the drug is added into an existing vehicle without optimisation of the formulation in terms of the active delivery to its site of action. The work encompasses preliminary pre-formulation studies, in vitro uptake and permeation studies using a model silicone membrane and pig ear skin. Moreover, the influence of topical formulations containing the model drug on the parameters indicative of skin health is tested in the in vivo studies. The primary objective is to optimise the skin delivery of NA with the use of appropriate excipients. The solvents are chosen on the basis of their physicochemical parameters, namely solubility parameter (δ), mutual miscibility and ability to dissolve the model drug. The performance of rationally developed simple formulations is tested in vitro and compared with prototype formulations containing more complex vehicles. In vitro uptake and permeation studies using silicone are performed to determine the influence of chosen solvents on NA permeation in a membrane which is less complex than skin. In addition NA skin delivery is evaluated with in vitro and in vivo techniques and the relationship between the physicochemical parameters of the solvents used and the drug percutaneous absorption is examined. Finally, the efficacy of prototype NA formulations in improving the skin state in vivo is investigated. The performance of prototype formulations in terms of NA percutaneous absorption is determined with reference to their influence on the skin condition.
Article
Falten reduzieren, die Haut straff halten und einen frischen Teint herbeizaubern — diese Versprechungen machen Cosmeceuticals. Sie enthalten meist effektivere Inhaltsstoffe als herkömmliche Kosmetika.
Article
Full-text available
In the present study, a chitosan (CS) derivative with the 2-(Methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SDAEM) zwitterionic monomer was prepared through chemical modification. The successful synthesis of CS-SDAEM was confirmed by Fourier-transform Infrared (FTIR) and Nuclear Magnetic Resonance (1 H-NMR) spectroscopies. Its crystallinity was studied by X-ray Diffraction (XRD), while in vitro cytotoxicity and cell viability assays established its biocompatibility. Filtered fresh pomegranate juice (PJ) was loaded in nanoparticles of neat CS and its derivative via ionic gelation method. Dynamic Light Scattering (DLS) revealed nanoparticles sizes varying between 426 nm and 4.5 µm, indicating a size-dependence on the polymer concentration used during encapsulation. High-performance liquid chromatography coupled with photodiode array and electrospray ionization mass spectrometry detection (LC-PDA-ESI/MS) revealed that PJ active compounds were successfully and in sufficient amounts encapsulated in the nanoparticles interior, whereas XRD indicated a crystalline structure alteration after nanoencapsulation. The resulted PJ-loaded nanoparticles were further utilized for the preparation of innovative O/W cosmetic emulsions. All produced emulsions exhibited good pH and viscosity stability for up to 90 days, while the sun protection factor (SPF) was enhanced due to the presence of the PJ. Enhanced antioxidant and antimicrobial properties due to the phenolic compounds of PJ were also observed.
Article
Within the field of cosmetic dermatology, several promising developments utilize artificial intelligence to better patient care. While many new treatments in cosmetic dermatology feature components of artificial intelligence, there is a knowledge gap within the field regarding the current and developing products featuring AI. We aim to highlight current and developing applications of artificial intelligence in cosmetic dermatology and provide insight into future modalities in this field. Methods include literature review, including peer-reviewed journal articles as well as product websites. In an age of medical and technological advancement, the utility of artificial intelligence models continues to grow.There are many new facets of artificial intelligence in cosmetic dermatology, marketed to both the consumer and the physician. With the development of customizable skin care, augmented reality applications, and at-home skin analysis tools, patients are empowered to be the masters of their cosmetic care. Artificial intelligence is utilized by physicians in new ways in their practices, with the advent of models for prediction of clinical outcome to treatments and tools for in-depth analysis of the patient's skin. Further research is required in the development of automated energy-based treatment devices and robotic-assisted treatments. Models for AI in cosmetic dermatology serve to increase patient involvement in their skin care decisions and have the ability to enhance the patient-physician experience. Dermatologists should be well-informed of the emerging technologies to better educate patients and enhance their clinical practice.
Article
The exposome has an impact on skin from life-long exposure. Acute short-term exposure to exposome stressors can also alter skin functions such as skin physical barrier and immune defenses, leading to skin dryness, sensitivity, flares of inflammatory skin conditions, or viral reactivations. Probiotics are defined as live microorganisms, which, when administered in adequate amounts, confer a health benefit on the host. An extract produced by lysing Vitreoscilla filiformis (VfeV) cultured in Vichy volcanic mineralizing water (VVMW) has properties of probiotic fractions. In this review, we present in vivo and ex vivo studies with a dermocosmetic formulation containing 80% VVMW, 5% VfeV, 4% niacinamide (vitamin B3), 0.4% hyaluronic acid, and 0.2% vitamin E (M89PF) to evaluate the clinical efficacy in preventing and repairing stressed skin. Skin barrier benefits of M89PF were shown in studies after the skin was exposed to sudden thermal changes, after skin irritation by tape stripping, and in sleep-deprived women. M89PF significantly accelerated skin renewal compared to untreated skin. Skin antioxidant defense activity of M89PF was shown after exposure to stress from UVA plus cigarette smoke aggression. Skin microbiome recovery after acute stress from a harsh cleanser was significantly better in M89PF-treated skin compared to bare skin. Clinical benefits of M89PF on correcting clinical signs of stressed skin were shown in both Caucasian and Asian women exposed to a stressful lifestyle and various external (pollution, tobacco smoking, solar radiation) and internal (poor sleep, stressful work, unbalanced diet, and alcohol consumption) exposome factors. M89PF also showed depigmenting properties on dark spots in Asian women. Further clinical studies are now warranted to evaluate the efficacy of M89PF as adjuvant care to prevent and repair skin barrier disruption and reinforce skin defenses in skin exposed to acute stresses.
Article
Background Sonophoresis can increase the delivery efficiency of various drugs into the skin. A recent advance in sonophoresis is the use of ultrasound-responsive liquid-core nuclei (URLN) to increase the probability of cavitation. In this study, we developed a URLN and ultrasound device, and demonstrated its effectiveness through in vitro and clinical tests. Materials and methods Three types of experiments were designed to evaluate the efficiency of sonophoresis with URLN. First, a Franz diffusion cell with cosmetic ingredients was used to analyze quantitatively the amount of drug delivered to the porcine skin. Second, after the application of sonophoresis with URLN, the porcine skin surface was examined using scanning electron microscopy (SEM) to see the changes in morphology. Finally, a clinical test was performed to verify the utility of sonophoresis with URLN. Results The results indicate that sonophoresis with URLN can increase the amount of compound delivered by approximately 11.9-fold over 6 h for niacinamide and by 7.33-fold over 6 h for adenosine. In addition, we observed approximately 20–30 μm sized pores on porcine skin in SEM images. In clinical testing, the application of sonophoresis with cosmetics containing URLN for 3 min improved the efficiency of transdermal drug delivery by 1.9-fold, the depth of absorption by 2.0-fold, and the speed of absorption by 2.0-fold at 30 min after application. Conclusion We expect that sonophoresis with specialized URLN in transdermal drug delivery could be used widely for various skin-related applications.
Article
The cosmetic industry is dynamic and ever-evolving. Especially with the introduction and incorporation of nanotechnology-based approaches into cosmetics for evincing novel formulations that confers aesthetic as well as therapeutic benefits. Nanocosmetics acts via numerous delivery mechanisms which involves lipid nanocarrier systems, polymeric or metallic nanoparticles, nanocapsules, dendrimers, nanosponges,etc. Each of these, have particular characteristic properties, which facilitates increased drug loading, enhanced absorption, better cosmetic efficacy, and many more. This article discusses the different classes of nanotechnology-based cosmetics and the nanomaterials used for their formulation, followed by outlining the categories of nanocosmetics and the scope of their utility pertaining to skin, hair, nail, lip, and/or dental care and protection thereof. This review also highlights and discusses about the key drivers of the cosmetic industry and the impending need of corroborating a healthy regulatory framework, refocusing attention towards consumer needs and trends, inculcating sustainable techniques and tenets of green ecological principles, and lastly making strides in nano-technological advancements which will further propel the growth of the cosmetic industry.
Article
Background Intense pulsed light therapy (IPL) decreases facial erythema and telangiectasias associated with rosacea. Topical skin care products decrease facial erythema by the action of active ingredients and masking effects. Objectives To assess the efficacy and tolerability of combining a topical skin care regimen (TSCR) comprised of a multifunctional three‐in‐one facial cream and a mineral‐based brush‐on SPF50 powder sunscreen with a single IPL treatment for treating mild‐to‐severe facial redness associated with rosacea. Methods Twenty female subjects with Fitzpatrick skin types I‐III received TSCR monotherapy for 12 weeks. At that time, subjects received a single IPL treatment and continued TSCR for 6 additional weeks. Subjects were evaluated at Baseline and at Weeks 4, 8, 12, and 18. Results Using a 7‐point redness scale, the overall mean (SD) redness score significantly improved from 3.05 (0.97) at baseline to 2.05 (0.76) at Week 18 (P < 0.01). There was a decrease in investigator‐rated erythema from baseline (bare skin) to Week 12 (bare skin, before IPL) when TSCR was used as monotherapy which did not achieve significance (P = 0.12). Most subjects (80%) were satisfied or Very satisfied with the TSCR at Week 18. All subjects (100%) agreed that it improved their baseline skin redness and most (85%) would recommend TSCR to others. TSCR was well‐tolerated with no significant changes in skin dryness, scaling, or itching. Mild burning occurred immediately following the IPL treatment at Week 12. Conclusion TSCR in combination with a single IPL treatment produced a significant improvement in overall facial redness in patients with rosacea. Longer‐term treatment with TSCR may produce continued improvement.
Article
Full-text available
To investigate the contribution of glycation and oxidation reactions to the modification of insoluble collagen in aging and diabetes, Maillard reaction products were measured in skin collagen from 39 type 1 diabetic patients and 52 nondiabetic control subjects. Compounds studied included fructoselysine (FL), the initial glycation product, and the glycoxidation products, N epsilon-(carboxymethyl) lysine (CML) and pentosidine, formed during later Maillard reactions. Collagen-linked fluorescence was also studied. In nondiabetic subjects, glycation of collagen (FL content) increased only 33% between 20 and 85 yr of age. In contrast, CML, pentosidine and fluorescence increased five-fold, correlating strongly with age. In diabetic patients, collagen FL was increased threefold compared with nondiabetic subjects, correlating strongly with glycated hemoglobin but not with age. Collagen CML, pentosidine and fluorescence were increased up to twofold in diabetic compared with control patients: this could be explained by the increase in glycation alone, without invoking increased oxidative stress. There were strong correlations among CML, pentosidine and fluorescence in both groups, providing evidence for age-dependent chemical modification of collagen via the Maillard reaction, and acceleration of this process in diabetes. These results support the description of diabetes as a disease characterized by accelerated chemical aging of long-lived tissue proteins.
Article
Full-text available
The effects of all-trans retinoic acid on glycosaminoglycan (GAG) accumulation were determined in cultured primary human skin fibroblasts. Confluent cultures treated with retinoic acid accumulated less [3H]GAG than those without the compound, an effect with an apparent threshold of 10 nM which was dose dependent in the concentration range tested (0-10 microM). At 10 microM, the inhibition was 54%. Greater than 80% of the labeled macromolecular material was streptomyces hyaluronidase digestible in cultures labeled with [3H]acetate. The incorporation of H2[35S]O4 into chondroitin sulfate and dermatan sulfate was unaffected, as was total protein synthesis. Retinol also inhibited accumulation of [3H]GAG, but was far less potent. T3 and dexamethasone can inhibit [3H]hyaluronate synthesis. When retinoic acid was added to cultures treated with either of these hormones at concentrations that maximally inhibit [3H] GAG accumulation, there was a further decrease in the rate of macromolecular accumulation. The retinoic acid effect evolved over 24-48 h after addition to the culture medium. A pulse-chase study failed to demonstrate any effect on [3H]GAG degradation.
Article
• Patients with moderate to severe bullous pemphigoid are usually treated with systemic corticosteroids. Four patients were treated with tetracycline hydrochloride and niacinamide because of the steroid-sparing anti-inflammatory properties of these agents. An excellent clinical response free of side effects was observed in all patients. The lesions recurred whenever treatment was discontinued. It is believed that these drugs suppress the complement-mediated inflammatory response at the basement membrane zone by suppressing neutrophil chemotaxis and mediators of the inflammatory response in this bullous disease.
Article
We measured enzymic and non-enzymic antioxidants in human epidermis and dermis from six healthy volunteers undergoing surgical procedures. Epidermis was separated from dermis by currettage and antioxidants were measured by high-performance liquid chromatography (HPLC) or standard spectrophotometric methods. The concentration of every antioxidant (referenced to skin wet weight) was higher in the epidermis than in the dermis. Among the enzymic antioxidants, the activities of superoxide dismutase, glutathione peroxidase, and glutathione reductase were higher in the epidermis compared to the dermis by 126, 61 and 215%, respectively. Catalase activity in particular was much higher (720%) in the epidermis. Glucose-6-phosphate dehydrogenase and isocitrate dehydrogenase, which provide reduced nicotinamide adenine dinucleotide phosphate (NADPH), also showed higher activity in the epidermis than the dermis by 111% and 313%, respectively. Among the lipophilic antioxidants, the concentration of α-tocopherol was higher in the epidermis than the dermis by 90%. The concentration of ubiquinol 10 was especially higher in the epidermis, by 900%. Among the hydrophilic antioxidants, concentrations of ascorbic acid and uric acid were also higher in the epidermis than in the dermis by 425 and 488%, respectively. Reduced glutathione and total glutathione were higher in the epidermis than in the dermis by 513 and 471%. Thus the antioxidant capacity of the human epidermis is far greater than that of dermis. As the epidermis composes the outermost 10% of the skin and acts as the initial barrier to oxidant assault, it is perhaps not surprising that it has higher levels of antioxidants.
Article
Advanced glycosylation end products (AGEs) are a potentially useful marker for monitoring glycemic control, predicting the risk of diabetes- and aging-associated clinical complications, and monitoring the treatment of patients with micro- and macrovascular diseases, including retinopathy, atherosclerosis, nephropathy, and neuropathy. AGEs or AGEproteins are derived from nonenzymatically glycated proteins (Amadori products) after further cross-linking with other proteins and additional rearrangement. AGE-proteins can be assayed by either radioreceptor or immunoassays in blood and tissues. No commercial kit is available at this time. © 1993 Wiley-Liss, Inc.
Article
The purpose of the present study was to examine the effect of non-enzymatic glycosylation and subsequent heating on the browning of the plantar stratum corneum and the finger-nail, and to elucidate the pathogenesis of the yellow skin and the yellow nail seen in diabetic subjects. We incubated stratum corneum and nail from non-diabetics in 0 (control), 10 (only nail), 20 (only nail), 100 and 250 mM glucose buffer at 37 degrees C for 5 days. These glycosylated samples were dialysed against distilled water for 96 h. Distilled water was changed every 24 h. Then samples were dried for 24 h. The extent of non-enzymatic glycosylation was measured by furosine content. Each 5 mg of sample was hydrolysed by 6 N HCl and processed for measurement of furosine by high-performance liquid chromatography. The rest of each sample was stored at 37, 42 (only nail), 47 and 52 degrees C for 14 days. Browning of the stratum corneum was assessed macroscopically, and that of the nail by spectrophotometry. Based on their spectrophotometric reflectances. Munsell's scores (H = hue score, V = lightness score, C = saturation score) and (H + C)/V were calculated for objective evaluation of browning. Incubation of the stratum corneum and nail with glucose buffer increased their non-enzymatic glycosylation (furosine) dose dependently. Macroscopically, the browning of the stratum corneum was enhanced in proportion to the glucose concentration and storage temperature. However, samples incubated in 10 and 20 mM glucose and stored at 42 degrees C did not show visible browning. Munsell's score of the nail samples treated by glycosylation and heating showed increased hue and saturation but reduced lightness. (H + C)/V values of these nail samples were significantly higher than those of the control. We could not detect any fluorescence with Wood light in the browned samples. The present in vitro study demonstrated that the browning of the stratum corneum and the nail depended on the extent of both non-enzymatic glycosylation and storage temperature. We suggested a hypothesis that the non-enzymatic glycosylation and the storage temperature of the stratum corneum and the nail might be a contributory factor in the development of yellow skin and yellow nail in diabetic patients.
Article
Hyperglycemia is increasingly regarded as the cause of the diabetic complications, in particular via the ability of glucose to glycate proteins and generate Maillard browning products which cross-link proteins and render them brown and fluorescent in vitro. Similar changes occur in vivo to long-lived proteins in diabetes mellitus as well as in ageing. The evidence supporting this route of glucose toxicity is discussed in the context of the ability of glucose to oxidize in vitro (catalyzed by trace amounts of transition metal) generating hydrogen peroxide, highly reactive oxidants, and protein-reactive ketoaldehyde compounds. It is suggested that protein browning in vivo may not result from the reactions of glucose with protein but from the transition metal-catalyzed reactions of other small autoxidisable substrates, such as ascorbate, with protein. Overall, studies of glycation and protein browning suggest a critical role for oxidative processes perhaps involving decompartmentalized transition metals and a variety of low molecular weight reducing agents in diabetes mellitus and ageing.
Article
Patients with moderate to severe bullous pemphigoid are usually treated with systemic corticosteroids. Four patients were treated with tetracycline hydrochloride and niacinamide because of the steroid-sparing anti-inflammatory properties of these agents. An excellent clinical response free of side effects was observed in all patients. The lesions recurred whenever treatment was discontinued. It is believed that these drugs suppress the complement-mediated inflammatory response at the basement membrane zone by suppressing neutrophil chemotaxis and mediators of the inflammatory response in this bullous disease.
Article
Nonenzymatic glycosylation of protein may play some role in the development of diabetic complications. To study the association of nonenzymatically glycosylated protein in keratinized tissues with the prevalence of cutaneous manifestations frequently observed in diabetics, we measured furosine values of stratum corneum, nail and hair from 61 diabetics and assessed their cutaneous manifestations. The manifestation most frequently found in this study was 10 cases of pigmented pretibial patches. We did not detect significant correlations between the prevalence of any cutaneous manifestations and furosine values of any keratinized tissues. However, 11 of the 17 patients with yellow nail showed high nail furosine values. Our data suggest that nonenzymatically glycosylated protein levels in the keratinized tissues do not correlate with the prevalence of cutaneous manifestations in diabetics, but do not exclude a role in the formation of yellow nail.
Article
Deep phenol peels were done on 11 middle-aged white women with severe actinic damage. Subsequently, face lifts were carried out after periods of 1.5 to 20 years. This made it possible to obtain a full-thickness specimen extending several centimeters on either side of the border between peeled and unpeeled skin. In contrast to the markedly abnormal elastotic appearance of unpeeled skin, a new band of connective tissue 2 to 3 mm in width was laid down in the subepidermal region. Fine elastic fibers formed a dense network in the band of regenerated collagen. The disarray and cytologic abnormalities of sun-damaged epidermis were also largely corrected. Melanocytes were not eliminated, but melanin synthesis was evidently impaired, accounting for the bleaching effects. The effects of a phenol peel are very long lasting and adequately account for the effacement of wrinkles and obliteration of actinic keratoses, mottling, and freckling.
Article
We investigated the clinical, histologic, and molecular responses of normal human skin to all-trans-retinol (ROL) application, compared to those induced by topical all-trans-retinoic acid (RA), and measured ROL-derived metabolites. Up to 1.6% ROL, 0.025% RA in vehicle (70% ethanol/30% propylene glycol), or vehicle alone were applied in a double-blind fashion to normal buttock skin and occluded for 4 d. ROL produced from none to only trace erythema, which was clinically and statistically insignificant, whereas RA induced a significant 3.7-fold increase in erythema score compared to vehicle (n = 10, p < 0.01). However, ROL induced significant epidermal thickening (1.5-fold at 1.6% ROL, p < 0.01), similar to RA (1.6-fold at 0.025% RA, p < 0.01), relative to the vehicle. ROL, compared with vehicle, also increased mRNA levels of cellular retinoic acid binding protein (CRABP-II) and cellular retinol binding protein (CRBP) genes as determined by Northern analysis (5- 6-fold and 6-7-fold, respectively) and riboprobe in situ hybridization. CRABP-II and CRBP protein levels were also higher following ROL than vehicle treatment, as measured by ligand binding (3.2-fold, p < 0.001; n = 7) and Western analysis (3.6-fold, p < 0.003; n = 6), respectively. Epidermal retinyl ester (RE) content, measured after removal of stratum corneum, rose 240-fold (p < 0.005, n = 5) by 24 h of ROL occlusion. RA content, however, was undetectable or detectable only at trace amounts in all samples obtained at 0, 6, 24, and 96 h after ROL occlusion. Detectability of RA was not correlated with ROL treatment (compared to untreated normal skin, p = 0.86) or baseline skin ROL levels (average r = -0.1, p> 0.3).
Article
Systemic and topical antimicrobials are effective in the treatment of inflammatory acne vulgaris; however, widespread use of these agents is becoming increasingly associated with the emergence of resistant pathogens raising concerns about microorganism resistance and highlighting the need for alternative nonantimicrobial agents for the treatment of acne. Nicotinamide gel provides potent antiinflammatory activity without the risk of inducing bacterial resistance. In our double-blind investigation, the safety and efficacy of topically applied 4% nicotinamide gel was compared to 1% clindamycin gel for the treatment of moderate inflammatory acne vulgaris. Seventy-six patients were randomly assigned to apply either 4% nicotinamide gel (n = 38) or 1% clindamycin gel (n = 38) twice daily for 8 weeks. Efficacy was evaluated at 4 and 8 weeks using a Physician's Global Evaluation, Acne Lesion Counts, and an Acne Severity Rating. After 8 weeks, both treatments produced comparable (P = 0.19) beneficial results in the Physician's Global Evaluation of Inflammatory Acne; 82% of the patients treated with nicotinamide gel and 68% treated with clindamycin gel were improved. Both treatments produced statistically similar reductions in acne lesions (papules/pustules; -60%, nicotinamide vs. -43%, clindamycin, P = 0.168), and acne severity (-52% nicotinamide group vs. -38% clindamycin group, P = 0.161). These data demonstrate that 4% nicotinamide gel is of comparable efficacy to 1% clindamycin gel in the treatment of acne vulgaris. Because topical clindamycin, like other antimicrobials, is associated with emergence of resistant microorganisms, nicotinamide gel is a desirable alternative treatment for acne vulgaris.
Article
Topical tretinoin treatment of photoaged hairless mice has been shown in previous studies to stimulate formation of a subepidermal zone of new connective tissue characterized by enhanced collagen synthesis. The aims of this study were to localize and/or quantify elastin, fibronectin, and glycosaminoglycans in the same model. Hairless mice (Skh-1) were irradiated thrice weekly for 10 weeks with gradually increasing doses of ultraviolet (up to 4.5 minimal erythema doses per exposure) from Westinghouse FS-40 bulbs. Mice were then treated five times a week with either 0.05% tretinoin, the ethanol:propylene glycol vehicle, or nothing for another 10 weeks. Controls included mice sacrificed after 10 weeks of ultraviolet treatment and age-matched untreated animals. The distribution of elastin and fibronectin was examined by immunofluorescence microscopy, which revealed fine fibrils in the subepidermal zone in tretinoin-treated skin. A quantitative slot-blot immunobinding assay showed that tretinoin induced a threefold higher amount of tropoelastin compared with controls. Insoluble elastin content (desmosine levels) was similar in all groups. Although fibronectin content was increased by ultraviolet radiation, tretinoin treatment induced the largest increase. In contrast, the amount of glycosaminoglycans, although increased by UVB radiation, was reduced by tretinoin treatment.
Article
Diabetes mellitus is a common condition, and persons who have this ailment are commonly encountered by dermatologists and primary care physicians. Because glucose attaches to long-lived proteins, it may have a profound effect on the tertiary structure of the protein. Chronic hyperglycemia may be responsible for the pathogenesis of many diabetic complications. It has been suggested that increased cross-linking of collagen in diabetic patients is responsible for the fact that their skin is generally thicker than that of nondiabetics. Advanced glycosylation end-products are probably responsible for yellowing of skin and nails. Increased viscosity of blood caused by stiff red blood cell membranes results in engorgement of the postcapillary venules in the papillary dermis, which is detected as erythema of the face or as periungual erythema. It is suggested that these skin changes may eventually be used as a reflection of the patient's current (as well as past) metabolic status.
Article
Glycation and oxidation are spontaneous chemical modifications of body proteins. Usually these reactions have been studied separately by assessing their fluorescent final products. Glycation of protein and its related fluorescence increases during aging, whereas the level of the fluorescence related to protein adducts from lipoperoxidation side products is unknown. Moreover, no data on the fluorescence, at different wavelengths, connected to the two reactions in the same sample are available. Nevertheless recent in vitro studies support the possibility of an interaction between the two spontaneous reactions. In this study, we evaluated the modification of proteins due to glycation and to lipoperoxidation side products, by measuring their specific fluorescence levels in the collagen of 65 healthy Wistar rats during the aging process. The relationships among the fluorescence at different wavelengths were also reported. The fluorescence pattern of insoluble collagen was characterized by a tridimensional study after the incubation of insoluble collagen with probable precursors of protein glycation (ribose) and oxidation (malondialdehyde and hydroxynonenal); the maximum peaks of fluorescence were recognized and compared. An increase of all fluorescence intensities was observed in rat collagen during aging: the glycation-related ones (y370/440 = 28.3 e0.08x, r = 0.808, p < 0.01; y335/385 = 66.7 e0.06x, r = 0.798, p < 0.01) and the hydroxynonenal adduct-related (y356/460 = 44.3 e0.06x, r = 0.810, p < 0.01) were exponential, whereas that derived from MDA-adduct was almost linear (y390/460 = 17.7 + 4.1x, r = 0.661, p < 0.01). A different accumulation rate might explain this result. Significant correlation coefficients were found within the age-adjusted fluorescence intensities of both reactions, suggesting a close relationship between glycation and oxidation, besides a mutual influence due to the broad spectrum area. The in vitro study confirmed a good specificity of collagen fluorescence after incubation with a reducing sugar (ribose 0.5 M for 6 hours) for protein glycation, and after incubation with malondialdehyde (0.1 mM for 3 hours) for lipoperoxidation adducts; surprisingly enough hydroxynonenal (0.5 mM for 3 hours) significantly increased the fluorescence related to pentosidine-like products (335 nm excitation/385 nm emission) suggesting that this compound might be the precursor of products with a fluorescence similar to pentosidine or of pentosidine itself. The in vivo results of this study confirm that nonenzymatic reactions, glycation and oxidation, significantly modify collagen fluorescence during aging and can play a role in tissue damage related to age. The close relationships among fluorescences may be due to a reciprocal interconnection rather than to a parallel increase of both reactions during aging; this hypothesis is supported by the in vitro findings of this study.
Article
Ultraviolet (UV) B irradiation leads to a potent immunosuppression of the capacity to reject syngeneic, antigenic tumors. If this immunosuppression is critical for the development of most skin tumors, then its prevention should result in prevention of photocarcinogenesis. We previously showed a correlation between the inhibition of photoimmunosuppression and prevention of photocarcinogenesis by dl-alpha-tocopherol, tannic acid, or alpha-difluoromethylornithine. The current study was designed to determine whether topical nicotinamide, the active form of vitamin B-3, or niacin, prevents immunosuppression and skin cancer in UV-irradiated mice. In a passive transfer assay for immunosuppression, splenocytes from UV-irradiated mice enhanced the growth of antigenic tumor challenges in recipient mice. Treatment of the UV-irradiated mice with 40 mumol of nicotinamide twice weekly starting two weeks before UV irradiation and throughout the experiment prevented this immunosuppression. UVB irradiation consisted of five weekly 30-minute exposures to banks of six FS40 Westinghouse fluorescent sunlamps. Mice received approximately 6.2 x 10(5) J/m2 in the passive transfer assays and 1.09 x 10(6) J/m2 in the photocarcinogenesis studies. Application of nicotinamide to UV-irradiated mice reduced skin tumor incidence from 75% to 42.5% (p = 0.016, Cox proportional hazards analysis). Thus topical nicotinamide prevented the immunosuppression and skin tumor induction by UVB irradiation.
Article
Past studies have shown that topical treatment of suntxposed skin with all-trans retinoic acid improves the clinical and histologic appearance of the skin. This is mociated with a reduction in matrix metalloproteinase elaboration and with expression of a newly synthesized collagenous matrix. Whether retinoid therapy might have a similar impact on the appearance of intrinsically aged skin is not known. This study, using human skin in organ culture and epidermal keratinocytes and fibroblasts in monolayer culture, show that retinoic acid stimulates growth of both keratinocytes and fibroblasts and stimu-lates extracellular matrix production by the fibroblasts. Adult skin from sun-exposed and sun-protected sites responds equally well to retinoic acid, whereas neonatal skin is much less responsive under the same conditions. The implications of this are (i) that retinoids may be able to repair intrinsically aged skin as well as photoaged skin, and (ii) that retinoids modulate human skin cell function in a manner that is age-related, and not simply a response to photodamage. Journal of Investigative Dermatology Symposium Proceedings 3:57-60, 1998
Article
Solar elastosis is a hallmark of photoaged human skin and a prominent feature in experimentally produced photoaging in murine skin. The products of mast cells have been implicated in the development of photoaged skin. We evaluated whether products from mast cells mediate chronic UVB-induced changes in murine skin by employing a strain of mast cell-deficient mice, WWv. The responses in these mice were compared to those in BALB/c, another albino mouse strain. Mice were exposed three times per week to UVB radiation for 11 weeks; the total dose was 18.8 J/cm2. Irradiated WWv mice showed greater epidermal alterations than the irradiated BALB/c mice. In the dermis, a 3.6-fold increase in elastin content, as measured by desmosine, was produced in the UVB-treated BALB/c mice; in contrast, no difference was observed in elastin between UVB-treated and untreated WWv mice. Collagen content was not increased by UVB treatment in either strain, and the glycosaminoglycan content increased a similar amount in UVB-treated mice in both strains. The number of mast cells increased two-fold and the number of neutrophils increased six-fold in UVB-treated BALB/c mice compared to age-matched unirradiated controls. Neutrophils, as well as mast cells, were absent in untreated and UVB-treated WWv mouse skin. These results suggest that products of mast cells are important in the development of solar elastosis in murine skin either by directly inducing elastin production by fibroblasts or indirectly by mediating the presence of other cell types that produce products that increase fibroblast elastin production.
Article
Cutaneous hyperpigmentation occurs in multiple conditions. In addition, many Asian women desire a lighter skin colour. Thus, there is a need for the development of skin lightening agents. Niacinamide is a possible candidate. To investigate the effects of niacinamide on melanogenesis in vitro and on facial hyperpigmentation and skin colour in vivo in Japanese women. Melanin production was measured in a purified mushroom tyrosinase assay, cultured melanocytes, a keratinocyte/melanocyte coculture model, and a pigmented reconstructed epidermis (PREP) model. The clinical trials included 18 subjects with hyperpigmentation who used 5% niacinamide moisturizer and vehicle moisturizer in a paired design, and 120 subjects with facial tanning who were assigned to two of three treatments: vehicle, sunscreen and 2% niacinamide + sunscreen. Changes in facial hyperpigmentation and skin colour were objectively quantified by computer analysis and visual grading of high-resolution digital images of the face. Niacinamide had no effect on the catalytic activity of mushroom tyrosinase or on melanogenesis in cultured melanocytes. However, niacinamide gave 35-68% inhibition of melanosome transfer in the coculture model and reduced cutaneous pigmentation in the PREP model. In the clinical studies, niacinamide significantly decreased hyperpigmentation and increased skin lightness compared with vehicle alone after 4 weeks of use. The data suggest niacinamide is an effective skin lightening compound that works by inhibiting melanosome transfer from melanocytes to keratinocytes.
Article
Glycation is the nonenzymatic reaction of glucose, α-oxoaldehydes, and other saccharide derivatives with proteins, nucleotides, and lipids. Early glycation adducts (fructosamines) and advanced glycation adducts (AGEs) are formed. "Glycoxidation" is a term used for glycation process involving oxidation. Sural, peroneal, and saphenous nerves of human diabetic subjects contained AGEs in the perineurium, endothelial cells, and pericytes of endoneurial microvessels and in myelinated and unmyelinated fibres localized to irregular aggregates in the cytoplasm and interstitial collagen and basement membranes. Pentosidine content was increased in cytoskeletal and myelin protein extracts of the sural nerve of human subjects and cytoskeletal proteins of the sciatic nerve of diabetic rats were decreased by islet transplantation. Improved glycemic control of diabetic patients may be expected to decrease protein glycation in the nerve. Protein glycation may decrease cytoskeletal assembly, induce protein aggregation, and provide ligands for cell surface receptors. The receptor for advanced glycation and products (RAGe) was expressed in peripheral neurons. It is probable that high intracellular glucose concentration is an important trigger for increased glycation, leading to increased formation of methylglyoxal, glyoxal, and 3-deoxyglucosone that glycateproteins to form AGEs intracellularly and extracellularly. Oxidative stress enhances these processes and is, in turn, enhanced by AGE/RAGE interactions. An established therapeutic strategy to prevent glycation is the use of α-oxoaldehyde scavengers. Available therapeutic options for trial are high-dose nicotinamide and thiamine therapies to prevent methyglyoxal formation. Future possible therapeutic strategies are RAGE antagonists and inducers of the enzymatic antiglycation defense. More research is required to understand the role of glycation in the development of diabetic neuropathy.
Article
Among many important physiological functions played by NADH (the reduced form of beta-nicotinamide adenine dinucleotide) its antioxidative properties are remarkable. Acting directly as an antioxidant, NADH can effectively protect the cell and its membrane from destruction by free radicals. NADH can be stabilized as a suspension in hydrophobic ointments prepared in a way that prevents contact with atmosphere containing oxygen and water. We present the first report of NADH as a treatment for some inflammatory dermatoses. It was found that topical application of 1% NADH diluted in Vaseline ointment can be very effective in the treatment of rosacea and contact dermatitis. Since no adverse effects were observed, therapy with NADH can be viewed as a potential alternative to other established treatments.
Article
The accumulation of advanced glycation end products (AGEs) in retinal cells is known to be associated with the risk of diabetic retinopathy. To develop a model of AGE-related metabolic stress in retinal organ cultures, we investigated the accumulation of a typical glycoxidation product (N(epsilon)-[carboxymethyl] lysine [CML]) and its possible pro-apoptotic effects on different retinal cell populations. Retinal organ cultures (rat) were kept for 9 h in the Ames medium containing 0 (control), 5, 25, 50, 150, 300 and 800 micro M glyoxal. The expression of bax, active caspase-3, and the accumulation of CML were studied by using immunohistochemistry after the paraffin embedding of retinal explants. Apoptosis was studied using the terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick end labeling (TUNEL) test and electron microscopy. Alpha lipoic acid (alpha-LA), sodium metavanadate (NaVO(3)), N-acetylcysteine (NAC), aminoguanidine (AG), and nicotinamide (NA) were used to influence glyoxal effects in organ cultures. In cultured normal non-diabetic retinae, small amounts of CML and the apoptosis-promoting factors bax and active caspase-3 were present. CML, bax and active caspase-3 increased after incubation with glyoxal. Incubation with glyoxal (<300 micro M, 9 h) increased apoptotic events in all layers. At low glyoxal concentrations, we found a graded sensitiveness of the different layers: at 25 micro M 39.4% in GCL, 28.2% in INL, 11.9% in ONL. After 800 micro M glyoxal, approximately 50% of the cells in all layers of the retina were apoptotic. In the ONL, this ratio was reduced by NaVO(3) (17%), by AG (27%), by NA (24.8%), by NAC (25.2%), and by alpha-LA (33.5%). In the INL, AG (25.9%) produced the best result. In the GCL, NAC, NaVO(3) and AG reduced apoptosis. A-LA had no significant protective effect. The glyoxal-induced rapid formation of CML shows the ability of our retina model to simulate AGE-related effects in vitro. The dose-dependent expression of apoptosis-promotor molecules indicates that the apoptosis-inducing machinery starts in most retinal cells within 9 h. The neurotoxicity of glyoxal-induced AGE formation was shown by the significantly increased rate of cell death in the retina. The significant decrease of apoptotic events (P<0.01) indicates that antioxidants and AGE formation blocker can exert a differentiated cytoprotection for each of the retinal cell layers.
Wrinkle effacement by chemical peel
  • Dp Hannon
Hannon DP. Wrinkle effacement by chemical peel. AAD poster, 1991.
Effects of nicotinamide on levels of der-mis hydroxyproline in photoaging skin
  • Yu J-M Y Liu
  • N Xie
Yu J-M, Liu Y, Xie N, et al. Effects of nicotinamide on levels of der-mis hydroxyproline in photoaging skin. Huanjing Yu Jiankang Zazhi 2002;19:102–4..
Prevention of photoimmunesuppression and photocar-cinogenesis by topical niacinamide
  • Hl Gensler
Gensler HL. Prevention of photoimmunesuppression and photocar-cinogenesis by topical niacinamide. Nutr Cancer 1997;29:157–62.
Selected heritable diseases of domesticated animals Handbook of mouse mutations with skin and hair abnormalities
  • Dunstan Rw Kennis
Dunstan RW, Kennis RA. Selected heritable diseases of domesticated animals. In: Sundberg JP, editor. Handbook of mouse mutations with skin and hair abnormalities. Boca Raton (FL): CRC Press; 1994. p. 509–32.
Nicotinamide 4% gel for the treatment of inflammatory acne vulgaris
  • Griffiths
Griffiths CEM. Nicotinamide 4% gel for the treatment of inflamma-tory acne vulgaris. J Dermatol Treat 1995;6:S8–10.
Effects of nicotinamide on levels of dermis hydroxyproline in photoaging skin
  • Yu