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Niacinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier
Abstract
Stratum corneum lipids, particularly ceramides, are important components of the epidermal permeability barrier that are decreased in atopic dermatitis and aged skin.
We investigated the effects of nicotinamide, one of the B vitamins, on biosynthesis of sphingolipids, including ceramides and other stratum corneum lipids, in cultured normal human keratinocytes, and on the epidermal permeability barrier in vivo.
The rate of sphingolipid biosynthesis was measured by the incorporation of [14C]-serine into sphingolipids.
When the cells were incubated with 1-30 micromol L-1 nicotinamide for 6 days, the rate of ceramide biosynthesis was increased dose-dependently by 4.1-5. 5-fold on the sixth day compared with control. Nicotinamide also increased the synthesis of glucosylceramide (7.4-fold) and sphingomyelin (3.1-fold) in the same concentration range effective for ceramide synthesis. Furthermore, the activity of serine palmitoyltransferase (SPT), the rate-limiting enzyme in sphingolipid synthesis, was increased in nicotinamide-treated cells. Nicotinamide increased the levels of human LCB1 and LCB2 mRNA, both of which encode subunits of SPT. This suggested that the increase in SPT activity was due to an increase in SPT mRNA. Nicotinamide increased not only ceramide synthesis but also free fatty acid (2.3-fold) and cholesterol synthesis (1.5-fold). Topical application of nicotinamide increased ceramide and free fatty acid levels in the stratum corneum, and decreased transepidermal water loss in dry skin.
Nicotinamide improved the permeability barrier by stimulating de novo synthesis of ceramides, with upregulation of SPT and other intercellular lipids.
... It is widely used in topical skincare products due to its diverse benefits and safety profile 19 . It is established that NIA reduces transepidermal water loss and improves skin hydration and pliability 20,21 . These findings can be connected to both in vitro and in vivo studies, showing that NIA upregulates the biosynthesis of sphingolipids, including CERs and their precursors, as well as FFAs, and cholesterol 21 . ...
... It is established that NIA reduces transepidermal water loss and improves skin hydration and pliability 20,21 . These findings can be connected to both in vitro and in vivo studies, showing that NIA upregulates the biosynthesis of sphingolipids, including CERs and their precursors, as well as FFAs, and cholesterol 21 . NIA has also anti-inflammatory properties, benefiting conditions like acne, rosacea, and atopic dermatitis 22 . ...
... NIA is widely used in topical skincare products due to its satisfactory safety profile and diverse beneficial properties on the biological function of the skin [19][20][21][22][23][24][25][26][27][28] . However, biophysical studies on the direct effect of NIA on the SC hydration process and the molecular organization of the lipid matrix and soft keratin structures of the SC are missing. ...
Niacinamide (NIA) is widely used in skincare for its favorable safety profile, anti-aging effects, and proven clinical efficacy in treating various skin conditions. However, its direct impact on the hydration and molecular organization of the stratum corneum (SC), the primary skin barrier, remains unclear. This study examines how NIA influences the SC’s lipid matrix organization, soft keratin structure, and water sorption behavior across varying relative humidity (RH) levels. Using small- and wide-angle X-ray diffraction and dynamic vapor sorption measurements, we compared NIA-treated SC samples to untreated controls under different RHs. The main findings show that while NIA is non-hygroscopic, it enhances water uptake of the SC at high humidity (95% RH). At low humidity (60% RH), NIA swells the keratin monomer spacing, although the SC water content remains low, suggesting a plasticizing effect that could increase SC flexibility in dry conditions. NIA also modifies the diffraction intensities from the lipid matrix differently at 60% and 95% RH, implying that it interacts with the SC lipid matrix and influences the water distribution within the SC lipid and protein domains. These effects appear independent of the investigated dose regime, indicating a specific concentration threshold. Overall, NIA shows distinct interaction with keratin, swelling the spacing between keratin monomers in dry conditions, without acting as a traditional keratolytic agent.
... Lipikar Baume AP+M is a hydrating moisturizer, primarily consisting of water, niacinamide, shea butter and aquae posae filiformis. Niacinamide, an amide of vitamin B 3 (niacin), has anti-pruretic, anti-inflammatory, depigmenting and photo-protective properties [43,44]. In addition, it helps to protect the lipid barrier of the skin by increasing the biosynthesis of intercellular lipids [43,44]. ...
... Niacinamide, an amide of vitamin B 3 (niacin), has anti-pruretic, anti-inflammatory, depigmenting and photo-protective properties [43,44]. In addition, it helps to protect the lipid barrier of the skin by increasing the biosynthesis of intercellular lipids [43,44]. Shea butter contains lipids that are similar to those of the skin, thereby supporting the skin's natural lipid layers [45]. ...
... Paradoxically, this increase in epidermal water content can lead to dehydration and worsening of the scar [40]. However it is possible that moisturizers such as Lipikar Baume AP+M which lack adequate occlusion, provide improved protection against dehydration over time due to stimulation of barrier repair by inducing lipid synthesis in combination with an excellent dermatological tolerance [43,44,66]. ...
Background
The mainstay of non-invasive scar management, consists of pressure therapy with customized pressure garments often combined with inlays, hydration by means of silicones and/or moisturizers as well as UV protection. It is generally accepted that scar dehydration resulting from impaired barrier function of the stratum corneum and expressed by raised trans epidermal water loss (TEWL) values, can lead to increased fibroblast activity and thereby hypertrophic scar formation. However, there is no consensus on exactly what optimal scar hydration is nor on barrier function repair: by means of silicone sheets, liquid silicone gels or moisturizers. Occlusive silicone sheets almost completely prevent TEWL and have been shown to be effective. Nevertheless, many important disadvantages due to excessive occlusion such as difficulties in applying the sheets exceeding 10–12 h, pruritus, irritation, and maceration of the skin are limiting factors for its use. To avoid these complications and to facilitate the application, liquid silicone gels were developed. Despite a reduced occlusion, various studies have shown that the effects are comparable to these of the silicone sheets. However, major limiting factors for general use are the long drying time, the shiny aspect after application, and the high cost especially when used for larger scars. Based on excellent clinical results after using three specific moisturizers for scar treatment in our patients, we wanted to investigate whether these moisturizers induce comparable occlusion and hydration compared to both each other and the widely recognized liquid silicone gels. We wanted to provide a more scientific basis for the kind of moisturizers that can be used as a full-fledged and cost-effective alternative to silicone gel.
Methods
A total of 36 healthy volunteers participated in this study. Increased TEWL was created by inducing superficial abrasions by rigorous (20x) skin stripping with Corneofix® adhesive tape in squares of 4 cm². Three moisturizers and a fluid silicone gel were tested: DermaCress, Alhydran, Lipikar and BAP Scar Care silicone gel respectively. TEWL reducing capacities and both absolute (AAH) and cumulative (CAAH) absolute added hydration were assessed using a Tewameter® TM300 and a Corneometer® CM825 at different time points for up to 4 h post-application.
Results
There was an immediate TEWL increase in all the zones that underwent superficial abrasions by stripping. Controls remained stable over time, relative to the ambient condition. The mean percentage reduction (MPR) in TEWL kept increasing over time with Alhydran and DermaCress, reaching a maximum effect 4 h post-application. Silicone gel reached maximal MPR almost immediately post-application and only declined thereafter. The silicone gel never reached the minimal MPR of Alhydran or DermaCress. Hydration capacity assessed through CAAH as measured by the Corneometer was significantly less with silicone gel compared to the moisturizers. Compared to silicone gel Lipikar provided similar occlusion and the improvement in hydration was highly significant 4 h post-application.
Conclusion
Based on the results of both our previous research and this study it is clearly demonstrated that the occlusive and hydrative effect of fluid silicone gel is inferior to the moisturizers used in our center. Lipikar hydrates well but is less suitable for scar treatment due to the lack of occlusion. A well-balanced occlusion and hydration, in this study only provided by Alhydran and DermaCress, suggests that moisturizers can be used as a scar hydration therapy that replaces silicone products, is more cost-effective and has a more patient-friendly application.
... Topical use of niacinamide stabilizes the skin barrier, reducing transepidermal water loss and stimulating protein synthesis (filaggrin, keratin, involucrin) and ceramides, making it useful in the treatment of atopic dermatitis. Topical application of nicotinamide increased ceramide, free fatty acid, and cholesterol synthesis and decreased transepidermal water loss in dry skin [19], which are the main pathogenetic factors underlying the barrier defect of atopic dermatitis.An anti-inflammatory effect and reduction in production of a variety of inflammatory cytokines (IL-1β, IL-6, IL-8, TNF), have also been demonstrated which justifies its use in the treatment of acne, rosacea, and other skin inflammatory states [20]. Topical formulations of niacinamide can be used in the treatment of acne vulgaris; in a randomized double-blind, controlled trial, 160 patients with inflammatory acne were treated with 4% nicotinamide gel or 4% erythromycin gel twice a day for 8 weeks. ...
... Vitamin B3 Anti-inflammatory effect [20]; synthesis of proteins and ceramides important for the skin barrier and reduction in trans epidermal water loss [19]; contribution in DNA repair processes [22] Treatment of acne [21], atopic dermatitis [19], actinic keratosis [23], and prevention of skin cancers [22] and photoaging [24] Vitamin B8 Involved in the production of keratin [29] and in several metabolic pathways (gluconeogenesis, fatty acid synthesis, amino acid catabolism) [26] Treatment of seborrheic dermatitis [31] and several hair and nail disorders [29] Vitamin C Inhibition of reactive oxygen accumulation [32]; involved in collagen synthesis processes [34] Treatment and prevention of photoaging [36] and photocarcinogenesis [42] Vitamin D Immunomodulatory effect [45]; control of keratinocyte proliferation and calcium homeostasis [43]; reduction of UV-induced DNA damage [48] Treatment of psoriasis [45] and prevention of non-melanoma skin cancers [49] Vitamin E Antioxidant activity [54] and reduction in lipid peroxidation [53] Treatment of scleroderma [57], yellow nail syndrome [55], acne [56], and melasma [58]. Prevention of skin aging [33] Vitamin K Involved in the activation processes of some coagulation factors [59]; antioxidant activity [61••] Treatment of acute and chronic skin wounds [61••] and laser-induced purpura [62] Coenzyme Q10 Antioxidant activities against environmental aggressions; component of mitochondrial respiratory chain [64] Treatment of skin aging [65] subjected to stresses of different nature, and the resulting damage can be repaired through processes that require energy. ...
... Vitamin B3 Anti-inflammatory effect [20]; synthesis of proteins and ceramides important for the skin barrier and reduction in trans epidermal water loss [19]; contribution in DNA repair processes [22] Treatment of acne [21], atopic dermatitis [19], actinic keratosis [23], and prevention of skin cancers [22] and photoaging [24] Vitamin B8 Involved in the production of keratin [29] and in several metabolic pathways (gluconeogenesis, fatty acid synthesis, amino acid catabolism) [26] Treatment of seborrheic dermatitis [31] and several hair and nail disorders [29] Vitamin C Inhibition of reactive oxygen accumulation [32]; involved in collagen synthesis processes [34] Treatment and prevention of photoaging [36] and photocarcinogenesis [42] Vitamin D Immunomodulatory effect [45]; control of keratinocyte proliferation and calcium homeostasis [43]; reduction of UV-induced DNA damage [48] Treatment of psoriasis [45] and prevention of non-melanoma skin cancers [49] Vitamin E Antioxidant activity [54] and reduction in lipid peroxidation [53] Treatment of scleroderma [57], yellow nail syndrome [55], acne [56], and melasma [58]. Prevention of skin aging [33] Vitamin K Involved in the activation processes of some coagulation factors [59]; antioxidant activity [61••] Treatment of acute and chronic skin wounds [61••] and laser-induced purpura [62] Coenzyme Q10 Antioxidant activities against environmental aggressions; component of mitochondrial respiratory chain [64] Treatment of skin aging [65] subjected to stresses of different nature, and the resulting damage can be repaired through processes that require energy. ...
Purpose of review:
Skin is the main defense organ of the human body against external insults (ultraviolet radiations, infections by pathogenic microorganisms, and mechanical and chemical stress). The integrity and functions of the skin barrier are supported by an adequate supply of micronutrients, such as several vitamins. The purpose of this review was to analyze all vitamin-related skin problems.
Recent findings:
The World Health Organization has estimated that more than 2 billion people worldwide experience deficiencies in the intake of essential vitamins and minerals; the percentage of adults all over the world using daily vitamin supplements, for treatment or prevention of chronic disease, has increased very rapidly in recent years. In this review, 65 studies have been selected in order to examine the role of the main vitamins and their derivatives involved in maintaining the well-being of the skin and their use as prophylactic and therapeutic agents in the management of skin disorders.
... Niacinamide is a key enzyme of the sphingolipid synthesis. 20,21 Vitamin D is involved in synthesis and secretion of antimicrobial peptides. 22 Vitamin D also is a regulator of genes involved in skin barrier function. ...
... It has been shown to improve the skin barrier function by reducing trans-epidermal water loss. 20,21 It would be interesting to further explore potential beneficial effects of niacinamide in cAD. ...
Background
Immune‐mediated inflammatory diseases (IMIDs) are associated with an abnormal immune response, resulting in a disturbed homeostasis and chronic inflammation. Most canine dermatological IMIDs (cDIMIDs), such as allergies, autoimmune and immune‐mediated diseases, require long‐term treatment with immunosuppressive drugs with potential adverse effects. In general, nutraceuticals are thought to be safe. As a result, there is a tendency for the more frequent use of nutraceuticals in veterinary medicine.
Objectives
The aim of this review was to present evidence‐based proof for the use of various nutraceuticals in the treatment of cDIMIDs and, where possible, to provide conclusions to guide their use in veterinary dermatological practice.
Methods
A comprehensive literature search on common cDIMIDs and nutraceuticals was performed. Only peer‐reviewed articles published in English and related to the study topic were included. A total of 64 eligible publications were classified in five categories based on study design and substantively assessed on additional criteria such as standardisation of diets and number of included animals. For final appraisal, classification of major, minor or no evidence was used whereby efficacy was based on clinical outcome measurements.
Conclusions
Minor evidence for the beneficial use of several nutraceuticals, including essential fatty acids, niacinamide and probiotics, was found for treatment of specific cDIMIDs. These nutraceuticals may improve clinical signs or reduce the required dose of concurrent medication (e.g. drug‐sparing effect) in some dogs. Some nutraceuticals also may be used for long‐term maintenance therapy. Despite some promising findings, major evidence for the use of nutraceuticals in cDIMIDs is lacking, warranting further research.
... It has been found to upregulate ceramide, sphingolipid, free fatty acid, and cholesterol synthesis in human keratinocytes. Its efficacy has been translated in vivo with a reduction of dry skin appearance, TEWL [9] and increased keratinocyte differentiation [10]. More recently, niacinamide has been shown to mitigate the release of pro-inflammatory lipids, such as arachidonic acid and prostaglandin D2, during skin barrier disruption [11]. ...
... Products applied were the vehicle containing niacinamide at 3% on half of the face, and the vehicle containing 0.1% BA + 0.5% EN extracts (solute concentration) on the contralateral side. Inclusion levels of niacinamide were chosen according to levels reported in the literature for skin barrier benefits [9,37]. ...
Abstract: The Scandinavian region is home to a unique biome with endemic plant species. The aim
of this study was to explore this natural diversity and identify plant extracts providing positive skin
barrier effects. Six plant extracts were identified as starting material. Following biochemical screening,
two candidates outperformed the rest: Betula alba (BA) and Empetrum nigrum (EN). Quantitative
PCR analysis showed that BA and EN upregulated barrier genes, when used individually and in
combination. Betula alba increased AQP3 and OCLN protein expression, something niacinamide was
incapable of. Additionally, the skin barrier was strengthened, evidenced by inhibition of KLK5 and
hyaluronidase and showed strong antioxidant and anti-inflammatory activity through DPPH and
COX2 inhibition, respectively. A first split-face clinical study was conducted using the combination
of extracts versus placebo. There was a significantly better skin restructuring effect and corneocyte
cohesion on the side treated with combined extracts. A second split-face clinical study assessed the
combined extracts versus 3% niacinamide. Significant variations in skin hydration and TEWL were
observed in favor of the extract treated side. In conclusion, we identified a natural alternative to
niacinamide for improving skin barrier health, in Scandinavian plant extracts, which yield strong
performance, but at a lower concentration.
... During aging, the structural and functional integrity of the skin barrier is changed or disturbed [104]. Tanno et al. showed that in cultured human epidermal keratinocytes, nicotinamide could upregulate the synthesis of major components of skin barriers, such as ceramide, other sphingolipid fractions (glucosylceramide and sphingomyelin), free fatty acid, and cholesterol [105]. Supplementation of nicotinamide to cultured normal human epidermal keratinocytes increased the synthesis of involucrin and filaggrin, which are essential proteins for fully integral keratinized corneocytes [106]. ...
... Nicotinamide decreases ECM-degrading enzymes and increases collagen synthesis in dermal fibroblasts [100][101][102]. Nicotinamide enhances the structural and functional integrity of the skin barrier by increasing the synthesis of lipid components [105]. Although nicotinamide exhibits various biological activities, the evidence for the existence of a specific molecular target is not clear. ...
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.
... A novel multi-action emollient plus cream (EC [Dermoflan ® ; Meda Pharma S.p.A., a Viatris Company]) has been developed containing several agents that target the pathophysiology of AD. These agents include niacinamide and sterols to help restore the skin barrier function [20][21][22], licorice extract to reduce inflammation [23], laureth-9-polydocanol to reduce itching [24], and xylitol and galacto-oligosaccharide, prebiotics that inhibit the growth of harmful bacteria and promote the growth of beneficial bacteria such as Staphylococcus epidermidis, to maintain the natural skin microbiome [25][26][27][28]. ...
... The 2018 European guidelines for the treatment of AD define ECs as "topical formulations with vehicle-type substances and additional active, nonmedicated substances" [41], with emollients containing agents that target the pathophysiology of AD -such as the EC investigated here -having potential additional benefits for patients compared with classic emollients. The novel multi-action EC contains xylitol and galacto-oligosaccharide (which maintains the skin microbiome) [25][26][27], licorice extract (which reduces itch and erythema) [23], niacinamide (which restores barrier function) [20,21], and laureth-9-polydocanol (which reduces itch) [24]. The results of the in vitro and clinical studies reported here suggest that the role of emollients can extend beyond hydration. ...
Background:
Emollients capable of restoring the skin barrier function would extend their role beyond basic maintenance therapy in atopic dermatitis (AD).
Objectives:
Investigate the effect of a novel emollient plus cream (EC; Dermoflan®) on the skin barrier in vitro and in patients with mild-to-moderate AD.
Methods:
The effect of EC on the skin barrier recovery was evaluated using a tape-stripping (TS) model. After TS, organ cultures were treated with EC (undiluted or diluted 1:1 with water) and analyzed at 18-120 h using hematoxylin and eosin, Oil Red O, immunohistochemical, and immunofluorescent techniques. In a double-blind, randomized study, EC or placebo was applied once daily for 2 months to antecubital folds of the upper and lower limbs of patients with mild-to-moderate AD in clinical remission. Epidermal thickness, vascularization, and epidermal hydration were assessed by optical coherence tomography and corneometry, respectively, at baseline, and 1 and 2 months following treatment initiation.
Results:
Following TS, EC treatment significantly increased epidermal thickness and lipid content versus diluent in the skin organ culture, as well as claudin-1, involucrin, and caspase-14 expression, suggesting skin barrier repair. EC treatment also decreased keratin-16 expression and increased levels of Toll-like receptors 1 and 2 versus diluent, suggesting involvement in regulating the epidermal immune response. In 20 patients randomized 1:1 to EC or placebo, EC treatment at the elbow fold/popliteal fossa significantly decreased epidermal thickness after 2 months, and the number of blood vessels at the elbow fold after 1 and 2 months, versus placebo. EC significantly improved the skin hydration after 2 months versus baseline.
Conclusions:
This novel multi-action EC may help to restore epidermal homeostasis and improve the skin of patients with AD. Results indicate that this novel multi-action EC could be a valid adjuvant therapy in patients with AD. Key Message: Novel multi-action emollient cream helps to restore epidermal homeostasis and improves the skin affected by AD.
... The CLE serves as a scaffold for the lamellar organization of the extracellular lipid matrix. Courtesy of Thomas Schmitt, Halle University, DE. [15] and 5% [11] concentrations of niacinamide have been used in the past to evaluate its clinical efficacy. 3% was selected as an intermediary concentration in these studies. ...
... However, our proteomic work showed no deficiency in its mass levels in facial SC but we have not measured activity levels [19,21]. Niacinamide has been reported to increase keratinocyte ceramide biosynthesis [15] and, although it is speculative, it is highly likely that it also increases the expression of 12R-LOX and TG especially as niacinamide is reported to increase the gene expression of peroxisomal proliferator activated receptor-alpha (PPARa), a key nuclear hormone receptor involved in keratinocyte differentiation and corneocyte formation [22]. The development of a healthy SC involves a well-orchestrated series of enzymatic steps enabling lipid, natural moisturizing factor and CE formation and maturation [1]. ...
Age‐related differences in maturation parameters of corneocyte envelopes (size, hydrophobicity and rigidity) were examined at several facial test sites in young and old female Caucasians. In addition, the effect of topically applied niacinamide on these parameters was evaluated in a 4‐week placebo‐controlled study.
... Vitamin B3 deficiency can lead to a disease known as Pellagra [1]. Niacinamide has been used for anti-hyperpigmentation/anti-aging applications [2,3], as an anti-oxidant [4], improving skin barrier function [5], and for alleviating some skin conditions such as acne vulgaris [6] and dermatitis [7]. Niacinamide reduces hyperpigmentation and improves skin brightness by inhibiting the transfer of melanosomes from melanocytes to keratinocytes as found in clinical studies [8,9]. ...
Niacinamide, a derivative of vitamin B3, has been shown to reduce skin pigmentation (i.e., acting as a brightening agent) and inflammatory responses such as dermatitis and acne vulgaris. However, niacinamide is a hydrophilic compound and poor partitioning to the lipid matrix in the uppermost layer of the skin (the stratum corneum or SC) limits its delivery to the skin. This necessitates the use of penetration enhancers to increase its bio-availability. In this study, we used computer simulations to investigate the skin penetration of niacinamide alone and in combination with other brightening agents that are also shown to be skin penetration enhancers, namely undecylenoyl phenylalanine (Sepiwhite®), bisabolol, or sucrose dilaurate. Molecular dynamics simulations were performed to reveal molecular interactions of these brightening agents with a lipid bilayer model that mimics the SC lipid matrix. We observed minimal penetration of niacinamide into the SC lipid bilayer when applied alone or in combination with any one of the three compounds. However, when all three compounds were combined, a notable increase in penetration was observed. We showed a 32% increase in the niacinamide diffusivity in the presence of three other brightening agents, which also work as penetration enhancers for niacinamide. These findings suggest that formulations containing multiple brightening agents, which work as penetration enhancers, may improve skin penetration of niacinamide and enhance the effectiveness of the treatment.
... 27 Vitamin B3 (niacinamide), commonly used in dermo-cosmetic products, has been demonstrated to increase glucosylceramide and sphingomyelin levels, as well as stimulate the synthesis of ceramides by keratinocytes in patients with dry skin. 60 Vitamin B3 is also thought to combat skin dryness that can develop following topical retinoid treatment by attenuating the overexpression of aquaporin-3 through the inhibition of epidermal growth factor receptor and extracellular signal-regulated kinase. 68 Additionally, vitamin B3 is thought to soothe disrupted skin by attenuating oxidative stress and inflammatory responses. ...
Acne and sensitive skin can take a profound toll on patients' well‐being, which can be exacerbated if the conditions are experienced together. This narrative review aims to identify appropriate treatments to facilitate a holistic management approach to acne (One Acne™), sensitive skin, and acne‐induced sequelae and describe the role of treatments in improving skin quality. Topical retinoids are considered the preferred first‐line option for acne treatment by dermatologists, either as monotherapy or in combination with other treatments, because of their ability to target various aspects of the disease. Tretinoin, trifarotene, adapalene, and tazarotene have all been assessed in clinical studies for managing acne‐associated scarring, with varying success, with the latter three reported to improve skin quality. Moreover, some corrective procedures, e.g., injectable non‐animal stabilized hyaluronic acid (NASHA) fillers, have proven effective for treating acne scarring. Both treatment types may complement each other to provide optimal treatment outcomes and patient satisfaction, as observed in several patients receiving concomitant treatment with NASHA fillers/topical trifarotene. Adjunctive use of cleansers, moisturizers, and photoprotection‐containing ingredients such as vitamin B3, glycerin, or pro‐vitamin B3 may also complement drug/corrective treatments to reduce skin irritation and risk of scarring, as well as improve skin hydration, tone, and overall appearance. This narrative review highlights that comprehensive skincare regimens should be used throughout acne patients' journeys to reduce treatment‐related irritation, improve treatment outcomes, adherence, and satisfaction, and enhance overall skin quality. Patients with sensitive skin should choose tailored skincare products to maintain skin barrier integrity and restore skin function.
... 26 In addition, niacinamide increases ceramide levels, as well as free fatty acid levels in the stratum corneum, and reduces transepidermal water loss, thus improving cutaneous barrier function. 59 Niacinamide can also be used to improve skin pigmentation because it has been shown to inhibit the transfer of melanosomes to keratinocytes, and to improve skin surface irregularity through increased skin turnover. 60 Indeed, clinical studies have confirmed the effectiveness of niacinamide for improving the visible signs of aging, with improvements of skin appearance, texture and elasticity and reductions in wrinkles, hyperpigmentation spots, and redness. ...
Skin aging has long been considered a purely cosmetic problem. However, as life expectancy increases, skin aging is taking on a functional dimension that goes beyond cosmetics and appearance. Preventive or therapeutic strategies are needed to target cellular senescence, a key process underlying the alterations in skin function and appearance that occur with aging, as well as to address the age-related skin changes associated with ‘dermatoporosis’ and chronic skin insufficiency/fragility syndrome. Thus, given the need for effective anti-aging
roducts that improve both the appearance and function of the skin, it is essential to distinguish active ingredients that have been proven to be effective, among the large number of available over-the- counter cosmeceuticals. This brief review focuses on a core group of topical actives, describing their clinical effects on senescence and aging, and their molecular mechanisms of action. These actives include hyaluronic acid, which has hydrating and viscoelastic properties and has been shown to reduce skin atrophy; retinaldehyde, which activates retinoid eceptors and increases cutaneous elasticity; vitamins C and E, which provide stable oxidative protection; and niacinamide, which reduces inflammation and mitigates the effects of senescence.
... Lipikar ® Baume AP+M, which primarily consists of water, niacinamide, shea butter and aqua posae filiformis, is a hydrating moisturizer, which has an anti-pruritic and photo-protective properties mostly attributable to the incorporated niacinamide, which is an amide of vitamin B3 (niacin) [37,38]. Niacinamide has been demonstrated to be more effective than white petroleum in decreasing TEWL and increasing hydration [39]. ...
Non-invasive scar management typically involves pressure therapy, hydration with sili-cones or moisturizers, and UV protection. Moisture loss from scars can lead to hypertrophic scar formation. Pressure therapy reduces blood flow, fibroblast activity, and transforming growth factor beta 1 (TGF-β1) release. This study examined various moisturizers and liquid silicone gel's impact on microcirculation. 40 volunteers participated in a study where superficial abrasions were created to induce trans epidermal water loss (TEWL). Five moisturizers (TEDRA ® , TEDRA ® NT1, TEDRA ® NT3, Alhydran ® , Lipikar ®) and BAP Scar Care ® silicone gel were tested. TEWL, hydration, and blood flow were measured up to 4 h post-application. Results showed that silicone had the least impact on occlusion and hydration. Alhydran ® reduced blood flow the most, while Lipikar ® increased it the most. TEDRA ® NT1 had reduced flow compared to TEDRA ® and TEDRA ® NT3. All TEDRA ® products exhibited high hydration, and all but silicone showed good occlusion. Moisturizers influenced skin microcirculation, with some causing decrease, while others increased flow. However, the clinical impact on scarring remains unclear compared to the evident effects of hydra-tion and occlusion. More research is necessary to study moisturizers alone and with pressure therapy on scars, along with potential adverse effects of increased microcirculation on scars.
... Melatonin and its metabolites are free radical scavengers that help maintain genomic, cellular, and tissue integrity after UV exposure [27,28]. Niacinamide is a member of the vitamin B family that has multi-factorial benefits in aged skin, including enhancing barrier function [29], normalizing hyperpigmentation [30], and boosting the production of dermal matrix components that can smooth wrinkles [31]. The clinical efficacy and safety of this cosmetic formulation [tri-retinoid complex (3RC)] was assessed in a proof-of-concept open-label study. ...
Introduction:
Plants are a source of natural ingredients with retinol-like properties that can deliver anti-aging benefits without the side effects typically associated with retinoid use. We hypothesized that by combining two such analogs, bakuchiol (BAK) and Vigna aconitifolia extract (VAE), with the potent retinoid retinal (RAL), the anti-photoaging potential of RAL could be enhanced without compromising its skin irritation profile. The purpose of this study was to demonstrate that BAK and VAE potentiate the anti-photoaging activity of RAL.
Methods:
Gene expression profiling of full-thickness reconstructed skin was first used to examine the impact of BAK or VAE in combination with RAL on skin biology. Next, the irritative potential of this combination, and its capacity to reverse key signs of photoaging in an ex vivo model was assessed. Finally, a proof-of-concept open label clinical study was performed to evaluate the anti-photoaging capacity and skin compatibility of a cosmetic formulation (tri-retinoid complex; 3RC) containing this complex in combination with other well characterized anti-photoaging ingredients.
Results:
In vitro profiling suggested that combining 0.1% RAL with BAK or VAE potentiates the effect of RAL on keratinocyte differentiation and skin barrier function without affecting its skin irritation profile. When formulated with other anti-photoaging ingredients, such as niacinamide and melatonin, 3RC reversed ultraviolet radiation-induced deficits in structural components of the dermal extracellular matrix, including hyaluronic acid and collagen. In vivo, it led to a reversal of clinical signs of age and photodamage, with statistically significant improvement to skin firmness (+5.6%), skin elasticity (+13.9%), wrinkle count (-43.2%), and skin tone homogeneity (+7.0%), observed within 28 days of once nightly use. Notably, the number of crow's feet wrinkles was reduced in 100% of subjects. Furthermore, 3RC was very well tolerated.
Conclusion:
These data suggest that 3RC is a highly effective and well-tolerated treatment for photoaging.
... 15,16 Vichy volcanic mineralizing water (VVMW) is a highly mineralized water containing 15 minerals that confer antioxidant properties to strengthen the skin barrier and help protect the skin against exposome aggressions. 17 Niacinamide (vitamin B3) has been shown to have an exfoliating effect, reduce dark spots, improve skin barrier function, 18 increase lipid biosynthesis, and reduce TEWL 19,20 to improve skin hydration and wrinkles. 21 Vitamin C and vitamin E have antioxidant, photoprotective, and hydration benefits. ...
Background
The decline in estrogen levels from several years before (perimenopause) and during menopause has various negative effects, including skin specific issues, which often receive less attention than other menopausal symptoms despite having a significant negative effect on quality of life (QoL). The objective of this study was to evaluate the effectiveness of anti‐aging dermocosmetic products designed for women during the perimenopause and menopause.
Materials and methods
An open study of 101 perimenopausal women (no menstruation for 4–12 months or irregular menstruation for <5 years) and 101 menopausal women (no menstruation for >12 months), not taking hormone replacement therapy, was conducted. Adapted dermocosmetic regimens, specific to each group (day cream, night cream and serum), were applied for 56 days. Assessments included automatic artificial intelligence diagnostics of eight clinical facial signs, hydration and transepidermal water loss (TEWL), and a menopause skin QoL questionnaire.
Results
Mean age was 50 ± 3.9 years (range 41–57) and 59 ± 3.8 years (range 50–66) for the perimenopause and menopause groups, respectively. Significant improvements in wrinkles and vascular signs, increases in hydration, decreases in TEWL, and a positive impact on QoL were observed after 56 days of application of the respective dermocosmetic regimens for both the perimenopause and menopause groups.
Conclusion
The anti‐aging skin care products designed specifically for perimenopausal and menopausal women increased skin hydration and improved wrinkles with a positive impact on QoL.
... However, nicotinamide inhibits nitric oxide synthase mRNA induction in activated macrophages [6]. Nicotinamide increases the biosynthesis of ceramides by keratinocytes [7]. It is known that the sphingosine derived from degradation of surface ceramide inhibits protein kinase C (PKC) and decreases basal cell proliferation dependent on PKC [8]. ...
... Both niacinamide and CoQ10 have been shown to enhance skin barrier function. Niacinamide increases the levels of key structural proteins, such as filaggrin and involucrin, and promotes the synthesis of ceramides, crucial components of the stratum corneum lipid matrix [4,5]. CoQ10 helps maintain the integrity of cell membranes and supports lipid metabolism, contributing to skin barrier function [6]. ...
Niacinamide, a derivative of vitamin B3, and coenzyme Q10 (CoQ10), a component of the electron transport chain, are two molecules with potential benefits for skin health and longevity. This comprehensive review discusses the molecular mechanisms through which niacinamide and CoQ10 contribute to maintaining skin cell vitality and combating inflammatory stressors, both on the skin and within the body. Additionally, it highlights the synergy between these two ingredients in cosmetic formulations and potential interactions with other active ingredients. Evidence suggests that niacinamide and CoQ10 can improve skin barrier function, reduce inflammation, promote collagen synthesis, and mitigate the detrimental effects of ultraviolet radiation. These findings emphasize the importance of niacinamide and CoQ10 in supporting skin health, longevity, and their potential in optimized cosmetic formulations.
... An in vitro study showed that nicotinamide caused 2-3 fold increase in free fatty acids and 1.5-fold increase in cholesterol. 15 Nicotinamide has a potential role in the treatment of psoriasis because of its anti-inflammatory effect, inhibition of the expression of ICAM-1 and MHC-II, and production of IL-12, TNF-α, and IL-1. 16 As the Soteri Skin cream used in our study, contains nicotinamide along with essential ceramides that help in re-storing the skin pH and epidermal barrier; thereby, helping in the above mentioned conditions. ...
p class="abstract"> Background: Eczema, also known as dermatitis, is characterized by skin inflammation, which presents as pruritus, skin dryness and erythema. Soteri cream, which was used in the study, contains Helianthus annus oil, glycerin, sodium hyaluronate, niacinamide and various ceramides. Niacinamide upregulates epidermal ceramide synthesis; thereby, strengthening epidermal barrier.
Methods: The study was conducted on 30 patients in total, out of which, 5 patients were of scalp (3) and palmar psoriasis (2), 10 of eczema, 10 of atopic dermatitis and 5 of rosacea. The above patients were the ones coming to Aayna clinic for their respective skin concerns. After doing clinical examination and taking written consent, patients were given Soteri skin cream, to apply twice daily on the area of concern. Follow up was done fortnightly for a month. Patient’s assessment in follow up visits was done with clinical photographic, along with dermoscopic photographic assessment after a month and by filling proforma for effects and side effects using VAS and SCORAD score (for atopic dermatitis).
Results: Complete symptomatic and visual improvement was seen in 3 patients of eczema, 2 of rosacea, 1 of scalp psoriasis and 6 of atopic dermatitis.
Conclusions: Soteri skin cream with its unique formulation of ceramides and niacinamide resulted in significant improvement in psoriasis, hand and nummular eczema, atopic dermatitis and rosacea. It is a steroid free, valuable line of treatment for chronic eczema.
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... 21,22 Nicotinamide is also widely used as a cosmetic skin care ingredient for its whitening, antiaging, and skin barrier building properties. 23,24 The list was further extended to comprise 4aminopyridine, which is also known to enhance the release of presynaptic acetylcholine and increase the force of muscle contractions, thus behaving as an antagonist of the neuromuscular blockade effects of antibiotics. 25,26 Beside organic compounds already known to possess mild antimicrobial activity, a number of other cocrystallization partners have been selected by using data mining tools available within the Cambridge Structural Database, 27 and their stability evaluated by available computational methods. ...
The possibility of obtaining cocrystals of kojic acid with organic coformers has been investigated by both computational and experimental approaches. Cocrystallization attempts have been carried out with about 50 coformers, in different stoichiometric ratios, by solution, slurry, and mechanochemical methods. Cocrystals were obtained with 3-hydroxybenzoic acid, imidazole, 4-pyridone, DABCO, and urotropine, while piperazine yielded a salt with the kojiate anion; cocrystallization with theophylline and 4-aminopyridine resulted in stoichiometric crystalline complexes that could not be described with certainty as cocrystals or salts. In the cases of panthenol, nicotinamide, urea, and salicylic acid the eutectic systems with kojic acid were investigated via differential scanning calorimetry. In all other preparations the resulting materials were constituted of a mixture of the reactants. All compounds were investigated by powder X-ray diffraction; the five cocrystals and the salt were fully characterized via single crystal X-ray diffraction. The stability of the cocrystals and the intermolecular interactions in all characterized compounds have been investigated by computational methods based on the electronic structure and pairwise energy calculations, respectively.
... Several reports suggest that niacinamide may exert various effects on the skin: it acts as an anti-inflammatory agent in acne DOI: 10.26717/BJSTR.2020. 26.004323 19790 [6], as an antioxidant [7], prevents photo-carcinogenesis and photo-immunosuppression [8], and increases intercellular lipid synthesis [9]. The biological activities of niacinamide also include antimicrobial, photo-protection, lighting, and anti-pruritus [10]. ...
... Vitamin B 3 (Niacinamide) is perhaps the most studied in regard to treatment of skin inflammation and erythroses, calming irritation. Niacinamide exerts anti-inflammatory effects due to inhibition of proinflammatory factors, as well as its ability to increase the expression of serine palmitoyl transferase, the enzyme involved in ceramide synthesis [36]. Therefore, studies have been carried out to evaluate the protective effect of a cosmetic preparation with 4% niacinamide during radiotherapy, obtaining a significant improvement in symptoms [37]. ...
Cancer treatments have undergone significant advances in recent years, although they are not exempt from side effects, including skin toxicity. Different studies show that skin care for cancer patients can be effective in reducing sequelae such as inflammation, xerosis, skin rash, and radiodermatitis, among others. This is the reason why research is being carried out on the ingredients of cosmeceuticals for those indicated for oncological skin care. On the other hand, it is necessary to implement measures that improve the patient’s well-being and, therefore, thalassotherapy techniques and the marine environment could be an effective resource to achieve this goal. This article reviews the publications related to skin care after cancer treatment, including thalassotherapy techniques that can also contribute to well-being.
... aging, hyperpigmentation, acne, rosacea, psoriasis, pruritus, dermatitis, etc. [132,143]. It increases the biosynthesis of ceramides, as well as other stratum corneum lipids and thus enhances epidermal permeability barrier function [148]. Studies have shown that niacinamide modulated NFkB-mediated inflammatory response, which could support its antiaging activity [149]. ...
The pigment polymer, melanin is the major determinant of visible pigmentation of skin, hair, and eyes. Its synthesis within organelles called melanosomes in melanocytes and transfer to and distribution within keratinocytes in the epidermis regulates skin pigmentation. Sunlight and its ultraviolet radiation component have a well-established role in skin tanning, through increasing epidermal melanin. Additionally, linked to the pigmentary system are disorders of pigmentation, resulting in problems ranging from hypopigmentation to hyperpigmentation. This chapter provides an overview of the prominent hyperpigmentary manifestations such as post-inflammatory hyperpigmentation (e.g., that associated with acne), solar lentigo, melasma, and peri-orbital hyperpigmentation and recent advances in cosmetic interventions borne out of strong scientific understanding and consumer clinical studies.
... Nicotinamide has been shown to promote the function of the skin barrier by stimulating the expression of mRNA for serine palmitoyl-transferase. This is a key enzyme for the biosynthesis of sphingolipids, stimulating the biosynthesis of ceramide and other intercellular lipids of SC [214]. Ascorbic acid, or vitamin C, is also thought to lead to increased ceramide synthesis and skin barrier formation when applied topically [215]. ...
The global cosmetics market reached US800 billion by 2023, at around a 7% annual growth rate. The cosmetics industry is emerging as one of the fastest-growing industries of the past decade. Data shows that the Chinese cosmetics market was US450 billion. The influence of social media and the internet has raised awareness of the risks associated with the usage of many chemicals in cosmetics and the health benefits of natural products derived from plants and other natural resources. As a result, the cosmetic industry is now paying more attention to natural products. The present review focus on the possible applications of natural products from various biological sources in skin care cosmetics, including topical care products, fragrances, moisturizers, UV protective, and anti-wrinkle products. In addition, the mechanisms of targets for evaluation of active ingredients in cosmetics and the possible benefits of these bioactive compounds in rejuvenation and health, and their potential role in cosmetics are also discussed.
... Niacinamide is a precursor of enzyme cofactor groups, such as nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate [15]. It may have various effects on the skin as an anti-inflammatory agent in acne, an antioxidant, and a compound that prevents photoimmunosuppression and photocarcinogenesis [16][17][18]. Niacinamide is stable in heat and light and is well tolerated in the skin, whereas other forms of the vitamin B3 family induce uncomfortable skin flushing reactions [15,19]. Recent research has reported that topical niacinamide inhibits the transfer of melanosomes from melanocytes to keratinocytes [5]. ...
Background This study aimed to evaluate the efficacy and safety of a dissolving microneedle (DMN)-encapsulated niacinamide skin patch to reduce facial hyperpigmentation.Methods A split-face study was conducted between April and June 2022 in 17 patients treated with a DMN-encapsulated niacinamide skin patch, which was applied only on the right side of the face, while the left face remained free of a pigmentation-improving agent. A topical moisturizer and physical sunscreen were applied on both sides of the face for 2 weeks. We compared both sides of the face 2 weeks after applying the skin patch using an automatic skin analysis device to investigate skin pigmentation. The melasma severity scores of both sides were evaluated before and 2 weeks after application.Results A significant difference in the epidermal pigmentation score between pre-treatment and 2 weeks after treatment was noted on the right side (P<0.05), but not on the left side of the face (P>0.05). A significant difference in the melanin score between pre-treatment and 2 weeks after treatment was noted on the right side (P<0.05), but not on the left side (P>0.05) of the face. There was no significant difference in the melasma severity score on either side of the face between pre-treatment and 2 weeks after treatment (P>0.05).Conclusions The application of a DMN-encapsulated niacinamide skin patch to improve skin pigmentation may yield good outcomes and provide comfort to patients without any complications.
... 19,20 Apart from its antipruritic/ soothing effect, niacinamide increases the synthesis of natural lipids in the SC such as ceramides. 21,22 Dexpanthenol acts as a humectant, but also triggers protein/lipid synthesis and compensates for decreased SC hydration by reducing the increased stiffness of SC lipid lamellae and keratin filaments (i.e., it increases molecular mobility/fluidity of SC lipid lamellae and proteins) observed in dry skin conditions. 3,23 There is growing evidence that the cutaneous care of atopicprone skin sufferers should start at an early age with regular use of non-alkaline cleansers and moisturizers to maintain skin barrier function. ...
Background:
Gentle cleansing of the skin without further compromising its barrier function and moisture content, and being simultaneously devoid of adverse effects on the skin microbiome, are important features of body cleansers for atopic-prone skin sufferers. For this population, a new dexpanthenol-containing liquid cleanser (DCLC) was developed.
Methods:
Two prospective 4-week studies have been conducted. Study 1 investigated the effect of once-daily DCLC on stratum corneum (SC) hydration, transepidermal water loss (TEWL), skin pH, and skin microbiome (all on the volar forearm) in adult subjects with dry skin (N=44). Study 2 explored the cutaneous tolerability of DCLC and its effect on the microbiome biodiversity of the volar forearm skin in infants/children with atopic-prone skin (N=33, aged 6 months to 6 years). In the latter study, DCLC was applied 2-3 days/week in combination with an emollient applied at least twice-daily.
Results:
In Study 1, on day 29, the mean change in skin surface capacitance from baseline was significantly greater in the forearm test area treated with DCLC than in the contralateral test area (control) treated with water only (5.16 vs. 3.65 a.u.; p = 0.011), suggesting long-term SC hydration. DCLC use was not associated with changes in TEWL, skin pH, or microbiome biodiversity if compared to control. In Study 2, the 4-weeks' use of DCLC in combination with an emollient was well tolerated according to pediatrician skin assessment, and no flare-ups were recorded. The microbiome biodiversity did not shift during the study.
Conclusion:
These findings support the use of DCLC in subjects with atopic-prone skin.
... 6 SPT is the rate-limiting enzyme in the de novo synthesis of ceramides which are main components of intercellular lipids in the stratum corneum and play an essential role in skin barrier function. 7,8 IVL is a component of the epidermal cornified cell envelopes, which are significant components of the epidermal barrier. 9 Therefore, Alpha-KG is expected to promote skin hydration and barrier function by the activation of cell proliferation and the up-regulation of mRNA expression of these genes related to the maintenance of epidermal function. ...
Introduction:
The tricarboxylic acid (TCA) cycle is a key metabolic pathway for driving the generation of mitochondrial energy in all oxidative organisms. Alpha-ketoglutarate (Alpha-KG), a precursor of glutamine, is known as a crucial intermediate of the TCA cycle and plays a pivotal role in multiple metabolic processes. As a precursor of glutamate and glutamine, AKG acts as an antioxidant agent as it directly reacts with hydrogen peroxide with formation of succinate, water, and carbon dioxide; meanwhile, it discharges plenty of ATP by oxidative decarboxylation. Several studies reported that Alpha-KG is a key participant in the detoxification of reactive oxygen species and acts as an integral part of the oxidative defense machinery. However, few studies have been reported on the efficacy of Alpha-KG in the maintenance of skin functions. This study demonstrated that Alpha-KG has beneficial effects on skin hydration and barrier function and that fermentation is an effective way to enhance the synthesis of Alpha-KG in yeast, which possesses mitochondria.
Methods:
Evaluation of promoting effects on epidermal keratinocyte proliferation: Keratinocytes were incubated with a test sample, and the degree of proliferation was determined by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Evaluation of promoting effects on mRNA expression of genes related to skin hydration and barrier function: Keratinocytes were incubated with a test sample, and gene expression levels of filaggrin (FLG), serine palmitoyltransferase (SPT), and involucrin (IVL) were analyzed by real-time RT-PCR. Analysis of Alpha-KG in rice fermented liquid: Alpha-KG in rice fermented liquid was quantitatively analyzed by capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). Clinical study testing methods and VISIA testing: After 28 days of treatment use the cream with Alpha-KG and control sample without Alpha-KG, instrumentation measurements were adopted to assess skin wrinkles, texture, elasticity, and firmness, tested by the VISIA-CR.
Results:
Immediately after using the sample for D0, the skin wrinkles were significantly reduced by 23.64%. After using the sample for D7, the average clinical score of outer corner wrinkles was significantly reduced by 15.23%, and nasolabial groove wrinkles were significantly reduced by 25.68%. After using the sample for D56, the mean clinical evaluation score of crow's feet decreased significantly by 25.42%; the average score of clinical evaluation of skin firmness increased significantly by 41.40%; the skin gloss increased significantly by 28.67%.
Conclusion:
It was demonstrated that Alpha-KG is expected to promote skin hydration and barrier function by the activation of cell proliferation and the up-regulation of mRNA expression of genes related to the maintenance of epidermal function in in vitro tests. In order to develop a cosmetic ingredient including Alpha-KG, we focused on fermentation with yeast as an efficient production method of Alpha-KG and found that fermentation of rice with yeast efficiently produced Alpha-KG. Taken together, it is considered that rice fermented liquid containing Alpha-KG could be a promising ingredient for skin care products. Through the clinical testing, rice fermented liquid containing Alpha-KG could be a promising cosmetic ingredient for skin care products.
... In an in vitro study, niacinamide has shown to improve keratinocyte differentiation, while increasing the synthesis of ceramides, free fatty acids and cholesterol. These results prompted a clinical study, with 12 male volunteers, in which the topical application of 2% niacinamide improved the water content from the horny layer and the epidermal barrier function, by reducing transepidermal water loss [34]. In a clinical study with 28 patients who had atopic dermatitis, the efficacy of a cream containing 2% niacinamide was compared with petrolatum in terms of hydration, transepidermal water loss and desquamation index. ...
Objective
Sensitive skin is characterized by self-reported sensory perceptions in response to stimuli that should not provoke unpleasant sensations. Cosmetic products for sensitive skin are designed to minimize these symptoms. This study aims to unveil the most used active ingredients for sensitive skin in facial care products.
Methods
A pool of products whose label included the expressions “sensitive skin”, “reactive skin” or “intolerant skin” were analyzed. The active ingredients were identified from product compositions and ranked in descending order of occurrence. The scientific evidence regarding the mechanism of action and efficacy of each ingredient was also compiled.
Results
Eighty-eight products from 19 multinational brands were included. Niacinamide leads the top, followed by Avena sativa, allantoin, glycyrrhetinic acid and derivatives and Laminaria ochroleuca. Ingredients which can reduce skin inflammation and act on the skin barrier were used in more than half of the products analyzed. The clinical studies regarding the active ingredients used in these products remain sparse and lack methodological quality. Among the top ingredients, niacinamide, panthenol and acetyl dipeptide-1 cetyl ester were the only ones studied on volunteers having sensitive skin, while acetyl dipeptide-1 cetyl ester and palmitoyl tripeptide-8 were designed to act on the molecular targets involved in this condition.
Conclusion
This study reveals the most used active ingredients in cosmetic products for sensitive skin, as well as the scientific evidence supporting their efficacy and the mechanisms of action. This insight is meaningful for dermatologists and other health professionals to provide customized advice based on the symptomatology of individuals with sensitive skin, and for the formulation of cosmetic products and design of new active ingredients.
... 9 Niacinamide has a barrierprotective antipruritic e ect by acting on the key enzyme for sphingolipid synthesis, called serine palmitoyltransferase, which increases the rate of ceramide synthesis. 10 Niacinamide also inhibits cAMP-phosphodiesterase, stabilizes mast cells, and reduces histamine release, which has an antipruritic e ect. 11 FIGURE 9. Graph of postin ammatory hyperpigmentation score of acne skin. ...
ABSTRACT: Background. The combination of benzoyl peroxide and a new topical therapy, such as topical niacinamide, reduces facial sebum production and also has a skin-lightening effect. This combined treatment might lead to improved efficacy in the treatment of facial acne vulgaris while also promoting the resolution of postacne erythema and postinflammatory hyperpigmentation.
Objective. The primary objective was to evaluate and compare the clinical efficacy of topical 2.5% benzoyl peroxide plus 5% niacinamide and 2.5% benzoyl peroxide with cream base for mild to moderate facial acne vulgaris. Secondary objectives were to evaluate and compare clinical efficacy regarding postinflammatory hyperpigmentation, postacne erythema, reduction of facial sebum production, and side effects.
Methods. Patients with mild to moderate facial acne vulgaris and aged 18 to 40 years were enrolled. Treatment was randomly assigned to the left or right side of the face for 12 weeks. Both inflammatory and noninflammatory acne lesions were counted by a physician, and the postinflammatory hyperpigmentation score and postacne erythema score were calculated using an Antera 3D® camera (Miravex, Dublin, Ireland). Sebum casual level was measured using a Sebumeter® (Courage+Khazaka Electronic, Köln, Germany) every two weeks. Physician improvement score, patient satisfaction index, and side effects were assessed by evaluation forms every two weeks.
Results. At Week 12, the niacinamide group (5% niacinamide+2.5% benzoyl peroxide) showed significant reduction in both the acne lesion count and sebum casual levels from baseline (p=0.000 and p=0.001, respectively). The reduction in noninflammatory lesion count in the niacinamide group was better than that in the cream base group (2.5% benzoyl peroxide+cream base), with a statistically significant difference (p=0.004). However, the reduction in inflammatory lesions was not significantly different between the two groups. The sebum casual level in the niacinamide group was reduced faster than that in the cream base group. The postacne erythema score was reduced from baseline in both groups, with no statistically significant difference within or between the two groups. The postinflammatory hyperpigmentation score showed increases in both groups above the baseline, with a statistically significant difference in the cream base group (p=0.000) but no such difference in the niacinamide group (p=0.58). There was no statistically significant difference between the two groups. Furthermore, no statistically significant differences were found between the two groups at every follow-up visit in terms of physician improvement scale, patient satisfaction index, or side effects.
Conclusion. The combination of 2.5% benzoyl peroxide and 5% niacinamide is more effective than 2.5% benzoyl peroxide alone for mild to moderate facial acne vulgaris.
Keywords: Niacinamide, benzoyl peroxide, acne vulgaris
... Topically, NAM has an epidermal barrier function, antiaging properties, anti-inflammatory, and sebostatic activities, making it beneficial for treating several dermatological disorders such as psoriasis, actinic keratosis, acne, and rosacea. The NAD precursor of nicotinamide prevents the depletion of cellular energy and therefore has photoprotective and anticarcinogenic properties [2][3][4]. ...
Background: Topical nicotinamide (NAM) can reduce excessive melanin deposition in cell culture, by reversibly blocking the transfer of melanosomes from melanocytes to the adjacent keratinocytes. Thus, it has been increasingly used as a whitening agent.
Objective: To assess the efficacy and safety of topical nicotinamide used for the treatment of melasma and hyperpigmentation.
Methods: An electronic search for topical nicotinamide was carried out on Pubmed and Medline databases to identify studies that addressed this topic as a whitening agent. And to review the primary and secondary outcomes.
Results: A significant decrease in hyperpigmentation and increased skin lightness was found with the use of topical nicotinamide, compared with the vehicle In two small sample size clinical studies. Combined regimens including nicotinamide and other ingredients offer more synergistic effects than monotherapy.
Conclusion: Due to the lack of sufficient evidence, the use of nicotinamide for melasma remains controversial. Extended randomized, double-blind, placebo-controlled trials with long-term follow-up periods are needed to assess the efficacy of nicotinamide as a whitening agent.
... -7 of 10 et al. 63 Niacinamide has also been reported to improve skin barrier function and increase SC thickness in a dose dependent manner, 31 to improve corneocyte maturity, 64 and to be active against acne. 65 Dexpanthenol is a humectant and has been reported to improve SC hydration and to improve skin barrier function, [66][67][68] play an important role in the synthesis of free fatty acids 69 and in reducing keratinocyte growth factor overexpression which is important for correct differentiation. ...
Background
Topical moisturizing products are widely used to alleviate the problems associated with xerotic skin. Their use affects many properties of the stratum corneum (SC) in a complex and interrelated manner. The range of measurement techniques available to the researcher has increased in recent years. However, few studies have looked for correlations between the different techniques for assessing how aspects of xerotic skin change over time as a result of topical moisturizer usage.
Objectives
A 3‐week in vivo study using an oil‐in‐water based moisturizing product and an untreated site was conducted to determine the clinical significance of and any correlations between a range of different approaches for the measurement of skin lipid content and also skin hydration and visual grading of dry skin.
Methods
A range of traditional and more recently developed skin measurement techniques have been used to examine a variety of SC properties in normal and xerotic skin during topical moisturizer usage.
Results
In vivo confocal Raman spectroscopy and analysis of SC lipids from tape strips both showed an increase in SC lipid level and organization after 3 weeks of moisturizer usage on xerotic skin. Hydration, measured both optically and electrically, also increased and skin barrier function improved, with strong correlations between the different measures of dryness being observed.
Conclusions
Strong correlations were observed between the skin measurements for lipid assessment and skin hydration with regard to the assessment of xerotic skin, providing valuable new information for future in vivo clinical research into dry and atopic skin.
Keywords
biophysical assessment, skin barrier, skin hydration, topical moisturizers, Xerosis
... Since serine was present in the verum formulation, disorganization of the lamellar arranges in the depths of the SC could be attributed to an enhanced synthesis and release of ceramides form lamellar bodies of keratinocytes of the SG. This is because serine is a substrate of serine palmitoyltransferase, which is the rate controlling enzyme in the biosynthesis of ceramides [2,[56][57][58]. ...
The influence of a topically applied formulation containing components of natural moisturizing factor (NMF) on barrier-related parameters of the stratum corneum (SC) was investigated in vivo using confocal Raman microspectroscopy in a randomized, placebo-controlled double-blind study on 12 volunteers for 14 days. This method allowed for the elucidation of subtle differences between the verum and the placebo even though the components of the verum naturally occur in the SC. This differentiation is not possible non-invasively by conventional methods. In this study, we found that the applied verum and placebo formulations disrupted the equilibrium of water, NMF and lipids in the SC. The adverse effects of the formulation could be mitigated by incorporating it into a simplified supplementation of NMF molecules. As a long-term effect, the amount of strongly bound water increases at 30–40% SC depth (p < 0.05) and the amount of weakly bound water decreases at 30–40% SC depth (p < 0.05) for the verum. This supplement was also unexpectedly able to prevent intercellular lipids (ICL) disorganization in selected depths. In the long term, the verum treatment limited the lateral disorganization of the ICL to the upper 20% SC depth. Further research is required to elucidate the interplay of these factors in the SC, to better understand their contribution to the equilibrium and barrier function of the skin. This understanding of the interaction of these naturally occurring components could help in the future to develop and optimize topical treatments for diseases like psoriasis, atopic dermatitis, ichthyosis where the skin barrier is disrupted.
... This can be attributed to the presence of niacinamide in these emollients. It is known that niacinamide increases the biosynthesis of natural SC lipids [7,35]. Our finding is in agreement with a previous healthy volunteer study using another niacinamide-containing emollient [13]. ...
Three studies were conducted with three new dexpanthenol-containing emollients containing increasing lipid contents (Emollients 1–3) to assess their performances in healthy adults with dry skin. All three studies (N = 42 each) followed virtually the same design. A single skin application of the study product was performed followed by once-daily usage. Skin hydration, transepidermal water loss (TEWL), skin biomechanical properties, and lipid content of the stratum corneum (SC) were regularly assessed over the 28-day study period; a subset (N = 22) underwent a sodium lauryl sulfate (SLS) challenge prior to product application. All three emollients were well tolerated and showed good performances with only minor differences in instrumental measurements. After single and prolonged once-daily applications of Emollients 1–3 to dry skin and dry SLS-damaged skin, skin hydration significantly increased from baseline (BL) (by 38.1–72.4% in unchallenged skin, p < 0.001 for all three). This was paralleled by significant increases in skin elasticity parameters. Usage of Emollients 1 and 3 caused increases from BL in SC cholesterol (by 9.8–12.5%, p < 0.05 for both) and SC free fatty acid levels (by 3.7–26.3%, p < 0.05 for both) at the end of the study. No sustained effects on TEWL were recorded. Our findings support the once-daily use of all three emollients in adults with dry skin.
... As it is reported that lipid classes vary with depths of the SC, this alone maybe contributing to the observed changes [7]. Other studies including those using niacinamide-containing formulations are known to increase the total levels of all ceramide species [9]. As the Lipbarvis methodology only evaluates three classes of ceramides, it is important to compare the results of Stettler et al. with other treatments where increases in the levels of all the three main ceramides species are observed [10,11]. ...
The article of Stettler et al. [1] points out dry skin is still a major problem globally and as a result, truly multifunctional moisturizers, with ingredients that have multiple mechanisms of action, need to be developed to address the underlying changes in the (patho)physiology of the condition. This was the focus of Stettler et al. ‘Targeted dry skin treatment using a multifunctional moisturizer’. As a result, it is important to address the claimed product efficacy as a multifunctional moisturizer relative to those reported by others, especially to the claim of improving ‘overall epidermal differentiation’ from use of the formulation.
... Nicotinamide is gaining increasing attention because of its potential in treating atopic dermatitis and photocarcinogenesis, as well as its use in anti-skin ageing cosmetic products. In previous research, nicotinamide was found to increase the biosynthesis of ceramides and maintain the epidermal barrier in vivo [3]. According to the report, application of nicotinamide on human skin results in an increase in free fatty acids in the stratum corneum (SC), as well as reduction in transepidermal water loss. ...
Objective
Nicotinamide, also known as niacinamide, is a water‐soluble vitamin that is used to prevent and treat acne and pellagra. It is often found in water‐based skin care cosmetics because of its high water‐solubility. Nicotinamide is a small molecule with a molar mass of 122.1 g/mol. However, it has a hydrophilic nature that becomes an obstacle when it penetrates through the skin. The topmost layer of the skin, the stratum corneum, acts as a strong hydrophobic barrier for such hydrophilic molecules. The oil‐based formulations are expected to enhance the transdermal delivery efficiency of nicotinamide.
Methods
We have developed oil‐based microemulsion formulations composed of a squalane‐vehicle. Monoolein was used as an emulsifier that has a potential to enhance the nicotinamide delivery through the stratum corneum.
Results
Because the mean size of the emulsions measured by dynamic light scattering was 20.9 ± 0.4 nm, the microemulsion formulation was stable under the long‐term storage. Monoolein acted as a skin penetration enhancer, and it effectively enabled the penetration of nicotinamide through human abdominal skin, compared with nicotinamide in a phosphate buffered saline solution. The flux was increased 25‐fold. Microscopic imaging revealed that the hydrophilic bioactive compounds penetrated through the intercellular spaces in the epidermis.
Conclusion
The monoolein‐based microemulsion was transparent and stable, suggesting that it is a promising formulation for a transdermal nicotinamide delivery.
... Ceramides are important barrier lipids in preventing TEWL. Moisturizers may address ceramide deficiencies in AD by adding them to the formulation, by adding ingredients that can upregulate de novo ceramide production (e.g., urea [62,63], niacinamide [64]), or by changing the physiologic milieu to support and promote ceramide production (e.g., lactic acid [62,65]). ...
Twice-daily moisturization is recommended by international guidelines as the bedrock of the management of atopic dermatitis (AD). Moisturizers should be selected based on proven clinical effectiveness in improving the skin barrier and improving the symptoms of AD. We searched the PubMed database for clinical trials assessing daily moisturization for the treatment of AD published between 2006 and 2019. Studies had to assess the efficacy of commercially available moisturizers using objective measures of corneometry, transepidermal water loss, or incidence of flare as endpoints, and treatments had to be currently available to patients. Clinical studies showed that moisturization (typically twice daily) significantly improved the skin barrier in adults and children with AD. Longer-term flare studies showed that daily moisturization reduced the incidence of flares and extended the time between flares. Proactive moisturization of infants at high risk of developing AD may reduce its manifestation. Therapeutic moisturizers for AD are specifically formulated with ingredients that target symptoms of AD, such as itch, inflammation, or compromised skin barrier. The US FDA requires that any moisturizer available in the USA and claiming to treat AD must contain colloidal oatmeal. Healthcare providers can maximize compliance and outcomes by educating patients on the benefits of liberally applying a therapeutic moisturizer twice daily to support the skin barrier and help reduce the incidence of flares. Specific recommendations should be for clinically tested moisturizers evaluated using objective, validated skin assessments.
... Deficiency of essential fatty acids leads to scaliness of the skin and an increased water consumption, mainly due to disruption of the water permeability barrier and an increase in trans-epidermal water loss (Basnayake and Sinclair, 1956). Linoleic acid 18:2(n-6) is also selectively targeted for b-oxidation by the sebaceous cells as a unique energy source for their function (Pappas et al., 2002), while application of nicotinamide (Tanno et al., 2000) and L-lactic acid (Rawlings et al., 1996) produce similar effects. ...
Botanical oils have a long history of traditional use and are routinely applied to skin care. The focus of this review is to contrast the functionality of skin oils versus the differential biological and toxicological effects of major plant oils, and to correlate them to their compositional changes. In total, over 70 vegetable oils were clustered according to their lipid composition to promote awareness of health practitioners and botanical product manufacturers for the safety and efficacy of oil-based interventions based on their fatty acid profiles. Since multiple skin disorders result in depletion or disturbance of skin lipids, a tailored mixture of multiple botanical oils to simultaneously maintain natural skin-barrier function, promote repair and regeneration of wounded tissues, and achieve corrective modulation of immune disorders may be required. As bioactive constituents of botanical oils enter the human body by oral or topical application and often accumulate in measurable blood concentrations, there is also a critical need for monitoring their hazardous effects to reduce the possible over-added toxicity and promote maximal normal tissue sparing. The review also provides a useful tool to improve efficacy and functionality of fatty acid profiles in cosmetic applications.
... The molecule is naturally found in human cells as a precursor of the co-dehydrogenases NAD and NADP and participates in several biological oxidation -reduction reactions. NIA has been reported to demonstrate various effects in vitro, namely (i) increased cellular DNA synthesis (ii) repair of UV-induced DNA damage in human melanocytes (iii) promotion of synthesis of ceramides, free fatty acids and cholesterol in cultured human keratinocytes (iv) inhibition of melanosome transfer from melanocytes to keratinocytes in co-cultured cells and (v) decreased IL-8 production and inhibition of P. acnes induced inflammatory responses of human keratinocytes (Tanno et al., 2000;Hakozaki et al., 2002;Grange et al., 2009;Thompson et al., 2014). ...
Niacinamide (NIA) has been widely used in cosmetic and personal care formulations for several skin conditions. Permeation of topical NIA has been confirmed in a number of studies under infinite dose conditions. However, there is limited information in the literature regarding permeation of NIA following application of topical formulations in amounts that reflect the real-life use of such products by consumers. The aim of the present work was therefore to investigate skin delivery of NIA from single solvent systems in porcine skin under finite dose conditions. A secondary aim was to probe the processes underlying the previously reported low recovery of NIA following in vitro permeation and mass balance studies. The solubility and stability of NIA in various single solvent systems was examined. The solvents investigated included Transcutol® P (TC), propylene glycol (PG), 1-2 hexanediol (HEX), 1-2 pentanediol (1-2P), 1-5 pentanediol (1-5P), 1-3 butanediol (1-3B), glycerol (GLY) and dimethyl isosorbide (DMI). Skin permeation and deposition of the molecule was investigated in full thickness porcine skin in vitro finite dose Franz-type diffusion experiments followed by mass balance studies. Stability of NIA for 72 h in the solvents was confirmed. The solubility of NIA in the solvents ranged from 82.9 ± 0.8 to 311.9 ± 4.5 mg/mL. TC delivered the highest percentage permeation of NIA at 24 h, 32.6 ± 12.1 % of the applied dose. Low total recovery of NIA after mass balance studies was observed for some vehicles, with values ranging from 55.2 ± 12.8 % to 106.3 ± 2.3 %. This reflected the formation of a number of NIA degradation by-products in the receptor phase during the permeation studies. Identification of other vehicles for synergistic enhancement of NIA skin delivery will be the subject of future work.
... NAM can also reduce the size of actinic keratoses and lead to complete regression in some patients Drago et al., 2017). As well, topical NAM and NMN have been reported to increase stratum corneum and epidermal thickness and reducing trans-epidermal water loss (Jacobson et al., 2007;Tanno et al., 2000). NAM has also been used for the treatment of acne (Shahmoradi et al., 2013;Shalita et al., 1995), melasma (Navarrete-Solís et al., 2011), and pemphigus vulgaris (Iraji and Banan, 2010) with positive results. ...
Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that is present in all living cells. NAD+ acts as an important cofactor and substrate for a multitude of biological processes including energy production, DNA repair, gene expression, calcium-dependent secondary messenger signalling and immunoregulatory roles. The de novo synthesis of NAD+ is primarily dependent on the kynurenine pathway (KP), although NAD+ can also be recycled from nicotinic acid (NA), nicotinamide (NAM) and nicotinamide riboside (NR). NAD+ levels have been reported to decline during ageing and age-related diseases. Recent studies have shown that raising intracellular NAD+ levels represents a promising therapeutic strategy for age-associated degenerative diseases in general and to extend lifespan in small animal models. A systematic review of the literature available on Medline, Embase and Pubmed was undertaken to evaluate the potential health and/or longevity benefits due to increasing NAD+ levels. A total of 1545 articles were identified and 147 articles (113 preclinical and 34 clinical) met criteria for inclusion. Most studies indicated that the NAD+ precursors NAM, NR, nicotinamide mononucleotide (NMN), and to a lesser extent NAD+ and NADH had a favourable outcome on several age-related disorders associated with the accumulation of chronic oxidative stress, inflammation and impaired mitochondrial function. While these compounds presented with a limited acute toxicity profile, evidence is still quite limited and long-term human clinical trials are still nascent in the current literature. Potential risks in raising NAD+ levels in various clinical disorders using NAD+ precursors include the accumulation of putative toxic metabolites, tumorigenesis and promotion of cellular senescence. Therefore, NAD+ metabolism represents a promising target and further studies are needed to recapitulate the preclinical benefits in human clinical trials.
... In addition, NAM has excellent cosmetic and anti-aging effects on the skin. It increases skin hydration by improving skin-barrier function with enhanced levels of sphingolipids, free fatty acids, and cholesterol, key components of the epidermal permeability barrier in the stratum corneum (Tanno et al. 2000). Molecular mechanisms responsible for these changes are poorly understood, but one in vitro study showed that NAM treatment increased mRNA level of serine palmitoyltransferase, the rate-limiting enzyme in sphingolipid synthesis, in keratinocytes (Holleran et al. 1990). ...
Background
Nicotinamide (NAM) is a form of vitamin B3 that, when administered at near-gram doses, has been shown or suggested to be therapeutically effective against many diseases and conditions. The target conditions are incredibly diverse ranging from skin disorders such as bullous pemphigoid to schizophrenia and depression and even AIDS. Similar diversity is expected for the underlying mechanisms. In a large portion of the conditions, NAM conversion to nicotinamide adenine dinucleotide (NAD⁺) may be a major factor in its efficacy. The augmentation of cellular NAD⁺ level not only modulates mitochondrial production of ATP and superoxide, but also activates many enzymes. Activated sirtuin proteins, a family of NAD⁺-dependent deacetylases, play important roles in many of NAM’s effects such as an increase in mitochondrial quality and cell viability countering neuronal damages and metabolic diseases. Meanwhile, certain observed effects are mediated by NAM itself. However, our understanding on the mechanisms of NAM’s effects is limited to those involving certain key proteins and may even be inaccurate in some proposed cases.
Aim of review
This review details the conditions that NAM has been shown to or is expected to effectively treat in humans and animals and evaluates the proposed underlying molecular mechanisms, with the intention of promoting wider, safe therapeutic application of NAM.
Key scientific concepts of review
NAM, by itself or through altering metabolic balance of NAD⁺ and tryptophan, modulates mitochondrial function and activities of many molecules and thereby positively affects cell viability and metabolic functions. And, NAM administration appears to be quite safe with limited possibility of side effects which are related to NAM’s metabolites.
... Los investigadores creen que los efectos antiinflamatorios pueden mejorar la apariencia de la piel al reducir los sistemas de peroxidasa leucocitaria que pueden conducir a daños tisulares localizados. Tanno et al. (2000), mostró que la nicotinamida podría tener alguna utilidad en el tratamiento del envejecimiento cronológico al disminuir la pérdida de agua transepidérmica. ...
En el mundo la industria cosmética está avanzando de manera exponencial junto a otras disciplinas y se observa que la utilización de compontes químicos se está dejando atrás y se está optando por insumos de origen vegetal y animal. En el presente estudio se tomó al músculo del fémur de langosta migratoria sudamericana (Schistocerca piceifrons peruviana) como insumo para una crema cosmética elaborada con ingredientes naturales. Estudios realizados actualmente han demostrado el poder regenerativo de las patas traseras de Locusta migratoria manilensis, una especie de langosta semejante a Schistocerca piceifrons peruviana. Para determinar el efecto cicatrizante y regenerativo se tomó 5 ratas blancas de la línea Wistar, para cada tratamiento y se les indujo heridas de 1,5 cm de longitud en el dorso 2 mm de profundidad y se probó distintas concentraciones del músculo del fémur. El diseño experimental consistió en el Tratamiento 0, al 0 por ciento del músculo del fémur de langosta, Tratamiento 1 al 1 por ciento , Tratamiento 2 al 2 por ciento y Tratamiento 3, al 4 por ciento , por un periodo de 12 días. El análisis estadístico mostró que para los parámetros de variación en el área, longitud y ancho de herida no había variación entre tratamientos, sin embargo, para los días que se tardó en cicatrizar la herida, si había diferencia, resultando el tratamiento 2 como el que mejor respuesta tuvo con 4,4 días. El tratamiento que tuvo mayor variación en longitud y ancho de herida entre tratamientos fue el tratamiento 3.
... Pre-clinical published studies have shown that niacinamide has the potential for topical application in cosmetic preparations [6], where it can increase the levels of ceramides, free fatty acids and cholesterol in the SC [7], and decrease sebum production [8]. In clinical studies, topical preparations with niacinamide were shown to reduce sebum production [9], to be effective in subjects with oily skin [10], and to return the altered skin barrier to normal levels in subjects with acne [11]. ...
Objective:
A randomised study was designed to evaluate the potential cosmetic benefit of a biomimetic, niacinamide-containing moisturising cream in oily, blemish-prone skin.
Methods:
Healthy adult women with oily, blemish-prone skin were randomised to one of three treatment groups: test, control, or positive control. In the test group, subjects used the test product (containing 4% niacinamide), plus the standard cleanser (Simple® Kind to Skin Moisturizing Facial Wash). In the control group, subjects received no moisturiser but used the standard cleanser. In the positive control group, subjects used Vivatinell Acnecinamide® Gel Cream (containing 4% niacinamide) as a moisturiser and Neutrogena Visibly Clear® Spot Clearing Facial Wash (containing 2% salicylic acid) as a cleanser. The positive control regimen was included to provide a comparison for estimates of effect size. The primary objective was to evaluate skin moisturisation as a change from baseline in corneometer values at 8 hours for the test regimen versus the control regimen. Analysis of covariance was applied for the primary efficacy analysis.
Results:
A total of 132 subjects were randomised with 44 included in each treatment group. A significant difference was observed in the primary endpoint for the test regimen compared with the control regimen (least squares mean difference [95% CI]: 3.12 [0.68, 5.56], p=0.0128). A trend was observed in favour of the positive control regimen compared with the control regimen. Secondary measurements of moisturisation supported the primary efficacy outcome. Assessment of blemishes showed a significant difference between the test regimen versus the control regimen for change from baseline in mean total blemish count at Week 8 (least squares mean difference [95% CI]: -1.80 [-3.41, -0.19], p=0.0290). No statistical comparisons between the positive control group and the test group were performed.
Conclusion:
This study provides proof-of-concept evidence that a novel lamellar lipid moisturiser containing niacinamide, in combination with a standard cleanser, can help moisturise the skin and provide an overall improvement in the complexion appearance of people with blemish-prone skin.
Study registration:
NCT03093181.
... Herein we describe a series of in vitro studies designed to determine the barrier efficacy and molecular lipid structure of the phospholipid-ISIS structural lamellar formulations using water vapour transport rate (WVTR) and Fourier transform infrared (FTIR) spectroscopy, respectively. In addition, we have investigated the effects of added panthenol [18] and the putative peroxisome proliferator activated receptor alpha (PPAR-a) agonist palmitoylethanolamide (PEA) [19] on inflammatory mediators, and the effects of niacinamide (NAM) on nicotinamide adenine dinucleotide (NAD) production and keratinocyte differentiation [20][21][22]. Finally, we evaluated a new anti-redness (AR) day cream and AR serum containing these ingredients, first, through in vitro analysis of their anti-inflammatory properties, and subsequently, in clinical studies to determine the safety, tolerability, and efficacy of the products in subjects with winter xerosis-associated facial redness and sensitive skin. ...
Objective:
To demonstrate the in vitro activities of panthenol, palmitoylethanolamide (PEA), and niacinamide (NAM) and determine the biophysical properties, clinical safety, tolerability together with efficacy of two developmental anti-redness (AR) formulations containing these ingredients, in alleviating facial redness associated with winter xerosis in healthy volunteers with sensitive skin.
Methods:
The anti-inflammatory and skin protective properties of panthenol, PEA and NAM were evaluated in vitro. The physical properties of the AR formulations were analysed using measurement of water vapour transport rate (WVTR) and infrared spectroscopy. Clinical studies were performed between the months of December and April (2014-15) with efficacy assessed during the winter. Facial redness, irritation, sensitization potential, photo-irritation, and photo-sensitization were evaluated. Self-assessed adverse reactions were reported in diaries of use.
Results:
Panthenol and PEA reduced prostaglandin E2 , interleukin-6, and thymic stromal lymphopoietin levels in vitro, while NAM induced nicotinamide adenine dinucleotide (NAD) levels and the keratinocyte differentiation markers: filaggrin (2-fold increase, p < 0.001), loricrin (2-fold increase, p <0.05), involucrin (2 fold increase, p < 0.001) & peroxisomal proliferator activated receptor-alpha (1.5 fold increase, p < 0.05). The two AR products exhibited low WVTR (include changes and stats) and displayed an ordered lipid structure. The day cream formulation protected against ultraviolet B radiation in vitro. A total of 382 participants were included in clinical studies which showed the AR formulations significantly improved facial redness associated with winter xerosis (include improvements and stats). No irritation, sensitization, photo-irritation, photo-sensitization or product-related adverse reactions were observed or reported in the clinical studies.
Conclusion:
The new products significantly improved skin redness associated with winter xerosis in participants with self-perceived sensitive skin. Both products were well tolerated with a suitable safety profile for topical use in subjects with sensitive skin. This article is protected by copyright. All rights reserved.
Textile finishes have long been utilized to impart novel functional properties to fabrics. These functionalizations can be applied to substrates through various methods. However, one of the most prevalent forms of application is via encapsulation systems, which offer protection to the active ingredients against potential adversities. These microcapsule delivery vehicles find application across diverse fields, spanning pharmaceutical, cosmetic, and textile industries. Within the textile sector specifically, such structures enable the development of functionalized substrates that act as vehicles for active compounds, facilitating their interaction with the epidermis and enabling novel functionalities, such as cosmetic or medicinal effects. This project examines how these textile materials with biological functionalities can be incorporated into dermocosmetic products, representing an intersection between various areas of knowledge. The review emphasizes the potential of bioactive textile substrates, noting that the market for these delivery systems, in conjunction with the dermocosmetic sector, is expected to experience significant growth. The integration of textile materials with bioactive molecules is poised to drive innovations in both the textile industry and the health and skincare sectors.
Emollients are the mainstay maintenance treatment for atopic dermatitis (AD). A novel generation of emollients, ‘emollients plus’, containing active, non-medicated substances, has softened the distinction between emollients and topical drugs. A literature search for selected key words was performed using PubMed. Additional papers were identified based on author expertise. Whilst the inclusion of five components of an ideal emollient has been proposed, no such consensus exists for emollients plus and they can vary markedly in their composition and modes of action for AD treatment. This could have a profound effect on their clinical efficacy. The efficacy of emollients plus in restoring and maintaining skin barrier function has been demonstrated on multiple levels, with evidence reported for their effects on the physical and biochemical, microbial, immunological, and neurosensory barriers. When selecting an appropriate AD treatment approach, the safety profiles of the available topical therapies must be carefully considered. There are several proposed treatment approaches for AD, including preventive, proactive, intermittent, and synergistic approaches. Emollients plus may be effective not only as maintenance therapy for AD, but also when used synergistically with anti-inflammatory pharmacological therapies.
This study established an ex vivo skin test method, which can effectively test the whitening and moisturizing effects of facial mask products. Simulate the subject's process of applying a facial mask on the isolated skin sample for 15 min a day for 5 d. After the treatment, the isolated skin samples were made into skin tissue sections. Fontan-Masson staining was used to evaluate the whitening effect of the mask. AQP3, Claudin-1 and Filaggrin immuno-fluorescence staining were used to evaluate the moisturizing effect of the samples. The results showed that the mask can significantly reduce the melanin content in the epidermal layer and had a whitening effect. At the same time, the mask can increase the positive rate and fluorescence intensity of AQP3, Claudin 1 and Filaggrin, indicating that the mask has the effect of moisturizing and enhancing the epidermal barrier. The ex vivo skin test method also has great application potential in the other efficacy evaluation of cosmetics.
The outermost structure of the epidermis is the stratum corneum, and it forms the epidermal permeability barrier which prevents the loss of water and electrolytes. Corneocytes are formed by the terminal differentiation of the keratinocytes from the granular layer of the epidermis. Lamellar granules or bodies (LG or LB) are specialized lipid carrying vesicles formed in suprabasal keratinocytes, destined for delivery of the lipids in the interface between the corneocytes. Keratohyalin granules are irregularly shaped granules present in the granular cells of the epidermis, thus providing these cells the granular appearance. Epidermis also generates a spectrum of antimicrobial lipids, peptides, nucleic acids, proteases, and chemical signals that together forms the antimicrobial barrier. Epidermal lipids, the integral components of the permeability barrier, are synthesized and secreted by the keratinocytes in the stratum granulosum after processing and packaging into the LB. The human skin is constantly exposed to hostile environment.
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.
Falten reduzieren, die Haut straff halten und einen frischen Teint herbeizaubern — diese Versprechungen machen Cosmeceuticals. Sie enthalten meist effektivere Inhaltsstoffe als herkömmliche Kosmetika.
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.
Preparations representing populations of (a) basal and spinous cells, (b) granular cells, and (c) stratum corneum cells were obtained by successive treatments of epidermal slices from pig skin with dilute buffered trypsin solutions. Total lipids accounted for about 8% of the cell dry weight in each of the three populations. Phospholipids, which predominated in the basal and spinous cells, accounted for only 21% of the total lipids in the granular cells and less than 0.1% in the stratum corneum. The latter cells contained more cholesterol (23% of total lipid) than either the granular cells (18%) or the basal and spinous cells (8%). The proportion of ceramide was also much higher in the stratum corneum (17%) and granular cells (9%) than in the basal and spinous cells (1%). The relative amounts of glycosphingolipid (glucosylceramide) and cholesteryl sulfate in the total lipids of stratum corneum cells were less than half those in the granular cells and basal and spinous cells. A novel phospholipid was a major component (26% of total) of the phospholipids from granular cells. The compound, which was partially characterized, contained phosphorus, fatty acids, and glycerol (molar ratio 1:3:2) and appeared to be a neutral derivative of phosphatidic acid.
The biochemical signaling mechanisms involved in transducing the effects of tumor necrosis factor alpha (TNF alpha) and gamma-interferon (gamma-IFN) on leukemia cell differentiation are poorly defined. Recent studies established the existence of a sphingomyelin cycle that operates in response to the action of vitamin D3 on HL-60 cells and that may transduce the effects of vitamin D3 on cell differentiation (Okazaki, T., Bell, R., and Hannun, Y. (1989) J. Biol. Chem. 264, 19076-19080). The effects of TNF alpha and gamma-IFN on sphingomyelin turnover were determined, and the specificity and role of sphingomyelin hydrolysis in HL-60 human promyelocytic leukemia cells with 20% hydrolysis of sphingomyelin at 15 min, 40% hydrolysis at 30-60 min, and return to base line at 2 h. The hydrolyzed sphingomyelin (18 pmol/nmol total phospholipid) was accompanied by the concomitant generation of ceramide (11.2 pmol/nmol total phospholipid). gamma-IFN also caused reversible hydrolysis of sphingomyelin with onset at 1 h and peak effect at 2 h. This sphingomyelin cycle appeared to be specific to the monocytic pathway of HL-60 differentiation, since it was not activated by retinoic acid or dibutyryl cAMP, inducers of granulocytic differentiation, nor with phorbol myristate acetate, an inducer of macrophage-like differentiation. Addition of synthetic ceramide or bacterial sphingomyelinase induced monocytic differentiation of HL-60 cells. Cell-permeable ceramide also caused prompt down-regulation of mRNA for the c-myc protooncogene. The time course of c-myc down-regulation was consistent with the action of ceramide as the mediator of TNF alpha action. These results suggest that sphingomyelin turnover may be an important signaling mechanism transducing the actions of TNF alpha and gamma-IFN with specific function in cell differentiation.
Sphingolipids comprise approximately 25% of the stratum corneum lipids and are considered critical constituents of the epidermal permeability barrier. Whether sphingoid base structures are synthesized in the epidermis or whether they are derived from circulating or dermal sources is not known. We report here the initial characterization of serine-palmitoyl transferase (EC 2.3.1.50; SPT), the rate-limiting enzyme in the synthesis of sphingolipids, from cultured human neonatal keratinocytes. Subcellular fractionation studies demonstrated that 79% of the total cellular SPT activity was associated with the microsomes. The specific activity of keratinocyte SPT was 270 +/- 20 pmol/min per mg of microsomal protein, a level significantly higher than activities reported in other tissues. Keratinocyte SPT showed an apparent Km for L-serine of 0.40 (+/- 0.04 mM, with an alkaline pH optimum (8.2 +/- 0.4). Keratinocyte SPT utilizes palmitoyl-CoA preferentially over other saturated or unsaturated acyl-CoA substrates; increasing acyl-CoA chain lengths above C16 by one or two carbons was less detrimental to activity than similar decrements in chain length. Finally, the mechanism-based inhibitors L-cycloserine and beta-chloro-L-alanine, demonstrated potent inhibition of keratinocyte SPT activity, with 50% inhibitory concentrations of approximately 3.0 and 25 microM, respectively. In summary, we have found that cultured human neonatal keratinocytes contain unusually high levels of serine-palmitoyl transferase activity, and that the substrate specificity of keratinocyte SPT may determine the base composition of epidermal sphingolipids.
The treatment of HL-60 myelocytic leukemia cells with 1 alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) resulted in the activation of a neutral sphingomyelinase and in sphingomyelin turnover (Okazaki, T., Bell, R., and Hannun, Y. (1989) J. Biol. Chem. 264, 19076-19080). In this paper, the effects of 1,25-(OH)2D3 on the product of sphingomyelin hydrolysis, ceramide, and the possible function of ceramide as a lipid mediator of the effects of 1,25-(OH)2D3 on HL-60 cell differentiation were investigated. Treatment of HL-60 cells with 1,25-(OH)2D3 resulted in a time- and dose-dependent increase in ceramide mass levels. Ceramide levels peaked at 2 h following treatment of HL-60 cells with 100 nM 1,25-(OH)2D3 with an increase of 41% over base line. The mass of generated ceramide (13 +/- 2 pmol/nmol of phospholipid) agreed with the mass of hydrolyzed sphingomyelin (17 +/- 4 pmol/nmol of phospholipid). Cell-permeable ceramides with shorter N-acyl chains induced HL-60 cell differentiation at subthreshold concentrations of 1,25-(OH)2D3. Higher concentrations of cell-permeable ceramides potently induced HL-60 cell differentiation independent of 1,25-(OH)2D3. A 2-h exposure of HL-60 cells to N-acetyl-sphingosine was sufficient to cause differentiation. Morphologically, N-acetylsphingosine caused a similar monocytic differentiation of HL-60 cells as did 1,25-(OH)2D3. Exogenous ceramide was further metabolized to sphingomyelin and other sphingolipids, but no conversion to sphingosine was detected. Moreover, sphingosine and its analogs failed to affect monocytic differentiation of HL-60 cells in response to subthreshold 1,25-(OH)2D3, indicating that the effect of ceramide was independent of sphingosine generation. These studies demonstrate that ceramide is a lipid mediator that may transduce the action of 1,25-(OH)2D3 on HL-60 cell differentiation.
Sphingolipid metabolism was examined in human promyelocytic leukemia HL-60 cells. Differentiation of HL-60 cells with 1 alpha, 25-dihydroxyvitamin D3 (vitamin D3; 100 nM) was accompanied by sphingomyelin turnover. Maximum turnover of [3H]choline-labeled sphingomyelin occurred 2 h following vitamin D3 treatment, with sphingomyelin levels decreasing to 77 +/- 6% of control and returning to base-line levels by 4 h. Ceramide and phosphorylcholine were concomitantly generated. Ceramide mass levels increased by 55% at 2 h following vitamin D3 treatment and returned to base-line levels by 4 h. The amount of phosphorylcholine produced equaled the amount of sphingomyelin hydrolyzed, suggesting the involvement of a sphingomyelinase. Vitamin D3 treatment resulted in a 90% increase in the activity of a neutral sphingomyelinase from HL-60 cells. The inferred role of sphingomyelin hydrolysis in the induction of cell differentiation was investigated using an exogenous sphingomyelinase. When a bacterial sphingomyelinase was added at concentrations that caused a similar degree of sphingomyelin hydrolysis as 100 nM vitamin D3, it enhanced the ability of subthreshold levels of vitamin D3 to induce HL-60 cell differentiation. This study demonstrates the existence of a "sphingomyelin cycle" in human cells. Such sphingolipid cycles (Hannun, Y., and Bell, R. (1989) Science 243, 500-507) may function in a signal transduction pathway and in cellular differentiation.
During terminal differentiation, mammalian epidermal lipids undergo striking changes in both composition and distribution. Phospholipids and neutral lipids are replaced by a mixture of ceramides and neutral lipids organized in intercellular lamellar bilayers. Whether all of these lipids and/or whether specific lipid classes regulate permeability barrier function is not known. When hairless mice were treated with acetone, the degree of barrier perturbation (measured as transepidermal water loss, TEWL) increased linearly with the amount of lipid removed. Moreover, virtually all lipid species appeared to be removed by acetone treatment. In contrast, the nonpolar organic solvent, petroleum ether, while removing greater amounts of lipids, provoked lesser barrier abnormalities. As determined by both quantitative thin-layer chromatography and histochemistry, petroleum ether selectively extracted nonpolar lipids leaving sphingolipids and free sterols in place. In petroleum ether-treated animals, subsequent acetone treatment removed additional sphingolipids and produced a dramatic increase in TEWL. A linear relationship existed for the quantities of sphingolipid removed and degree of barrier disruption in acetone-treated, but not petroleum ether-treated animals. These results support a relationship between the total lipid content of the stratum corneum and barrier function. Secondly, although the results demonstrate the participation of the total lipid mixture in the barrier, removal of nonpolar species alone appears to cause only a modest level of barrier disruption, while removal of sphingolipids and free sterols leads to a more profound level of barrier perturbation.
The lipids of mammalian stratum corneum are known to be important regulators of skin permeability. Since the human stratum corneum displays remarkable regional variations in skin permeability, we assessed the total lipid concentration, the distribution of all major lipid species, and the fatty acid composition in Bligh-Dyer extracts from four skin sites (abdomen, leg, face, and sole) that are known to display widely disparate permeability. Statistically significant differences in lipid weight were found at the four sites that were inversely proportional to their known permeability. In all four sites, among the polar lipids, the stratum corneum contained negligible phospholipids, but substantially more cholesterol sulfate (1-7%) than previously appreciated. As in the stratum corneum from other mammals, the bulk of the lipids consisted of neutral (60-80%) and sphingolipids (15-35%). Of the neutral lipids, free sterols (4- to 5-times greater than esterified sterols), free fatty acids, triglycerides, and highly nonpolar species (n-alkanes and squalene) predominated. n-Alkanes, which were present in greater quantities than previously appreciated, comprised a homologous series of odd- and even-chained compounds ranging from C19 to C34. The sphingolipids comprised over 80% ceramides vs. lesser quantities of glycosphingolipids. In all four sites, the sphingolipids were the major repository of long-chain, saturated fatty acids. The neutral lipid:sphingolipid ratio generally was proportional to the known permeability of each site: higher neutral lipids and lower sphingolipids generally were associated with superior barrier properties. These studies provide: 1) the first detailed, quantitative analysis of human stratum corneum lipids and 2) information about the variability in lipid composition at four skin sites with known differences in permeability. The latter results suggest that variations in neutral lipids, rather than sphingolipids, may underlie local variations in skin permeability.
The enzyme serine palmitoyltransferase (SPT; EC 2.3.1.50), which catalyzes the first committed and rate-limiting step in sphingolipid synthesis, is up-regulated in the epidermis as part of the homeostatic repair in response to permeability barrier perturbation. Moreover, UVB exposure, which also perturbs the barrier, up-regulates sphingolipid synthesis, but the basis for this increase is not known. The recent isolation of cDNAs for SPT (i.e., LCB1 and LCB2) allow molecular regulation studies to be performed. Therefore, we determined whether UVB exposure alters mRNA, protein, or activity levels for SPT in cultured human keratinocytes (CHKs) as a mechanism for regulation of epidermal sphingolipid synthesis. In CHK, transcripts for both LCB1 (3.0 kb) and LCB2 (2.3 kb) are evident by Northern blot analysis, and UVB exposure (23 mJ/cm²) induces a delayed 1.8 to 3.3-fold increase in LCB2 mRNA levels (P < 0.01) 48 h after treatment versus non-irradiated control cells. In contrast, neither LCB1 nor a second LCB2 transcript (8.0 kb) changed significantly. Likewise, Lcb2 protein levels (by Western blot analysis), as well as SPT activity, increase in parallel with the increased LCB2 mRNA. Finally, incorporation of [¹⁴C]-acetate into sphingolipids was increased significantly 48 h after UVB treatment. Together, these results demonstrate that CHKs respond to UVB by increasing sphingolipid synthesis, primarily through increases in both LCB2 mRNA and protein levels, leading to increased SPT activity. These results demonstrate one mechanism (UVB) whereby SPT is regulated at the molecular level, and suggest further that epidermis up-regulates sphingolipid synthesis at both the mRNA and protein levels in response to UVB.
—Farrell, A. M., Y. Uchida, M. M. Nagiec, I. R. Harris, R. C. Dickson, P. M. Elias, and W. M. Holleran. UVB irradiation up-regulates serine palmitoyltransferase in cultured human keratinocytes. J. Lipid Res. 1998. 39: 2031–2038.
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Daily treatments of skin in hairless mice with concentrates of rice wine, Japanese traditional alcohol, lowered transepidermal water loss levels compared to the controls on the 3rd day after ultraviolet B (UVB) irradiation. These findings indicate that the concentrates of rice wine suppress the murine skin barrier disruption caused by UVB. Ethyl α-D-glucoside (α-ethylglucoside), one of the peculiar components in rice wine, showed the same effect, whereas β-ethylglucoside had no effect. In order to clarify the functions of α-ethylglucoside on murine skin, we examined the effects of this compound on the expression of some phenotypes in human keratinocytes in vitro. As a result, α-ethylglucoside as well as β-ethylglucoside enhanced cell proliferation weakly, and the formation of cornified envelopes and differentiated type keratin (K1) in keratinocytes was accelerated by α-ethylglucoside but not by β-ethyl-glucoside. From the results, we concluded that α-ethylglucoside enhanced the differentiation of keratinocytes, which might be related to reduced barrier disruption by UVB.
in the lower stratum comeurn but underwent degradation towards the upper surface of the stratum corneum. These observations contrasted with xerotic skin, which had disorganized lipid bilayers in the upper stratum corneum, although apparently normal lipid bilayers in the deeper tissue regions. Also, desmosomes remained undegraded in the upper layers of the xerotic stratum corneum, a finding corrobo- rated by western blotting showing increased levels of desmoglein 1. Chromatographic analysis of stratum comeurn lipids showed decreased ceramide and increased fatty acid levels in subjects with xerosis compared with normal individuals, particularly in the outer stratum corneum layers. Although ceramides were lost from the stratum comeurn, the increased levels of fatty acids may be due in part to the deposition of soap fatty acids. Our results support previous studies demonstrating the importance of desmosomal degradation in desquamation. Furthermore, we have been able to show changes in the normal membrane structure of intracellular lipids in the desquamating layers of the stratum comeurn. These studies also provide new insights into soap-induced winter xerosis, revealing abnormalities in stratum comeurn lipid composition and organization together with reduced desmosomal degradation.
As reviewed in this article, the stratum corneum must now be accorded the respect due to a structurally heterogeneous tissue possessing a selected array of enzymatic activity. The sequestration of lipids to intercellular domains and their organization into a unique multilamellar system have broad implications for permeability barrier function, water retention, desquamation, and percutaneous drug delivery. Yet, the functions and organization of specific lipid species in this membrane system are still unknown. Certain novel insights have resulted from comparative studies in avians and marine mammals. Further elucidation of the molecular architecture and interactions of lipid and nonlipid components of the stratum corneum intercellular domains will be a prerequisite for a comprehensive understanding of stratum corneum function.
Patients with atopic dermatitis (AD) often present with a dry skin. To clarify the relationship between dry skin and lipid abnormalities within stratum corneum, stratum corneum lipids were collected from six AD patients aged 15 to 25 years and from sex- and age-matched controls. All major stratum corneum lipid classes were separated and quantitated by high-performance thin-layer chromatography/photodensitometry. Six ceramide fractions were also isolated and quantitated by thin-layer chromatography/photodensitometry. Esterified fatty acids of both ceramide 1 (acylceramides) and wax esters were analysed by capillary gas chromatography. The relative amounts of all the stratum corneum lipid classes including squalene, cholesterol esters, wax esters, triglycerides, free fatty acids, cholesterol, ceramides, cholesterol sulphate and phospholipids did not differ statistically between AD patients and controls. However, a significant decrease in proportion of ceramide 1, which is believed to be a carrier of linoleate responsible for a water-barrier function, and increased levels of esterified C18:1 fatty acids (oleate) of ceramide 1 were observed in AD patients. On the other hand, the fatty acid compositions as well as the proportions of C16:1 straight-chain component in sebum wax esters of AD patients were very similar to those of controls. These results suggest that a significantly reduced amount and/or structural alterations of ceramide 1 deriving from epidermal keratinocytes may be responsible for the impaired water-barrier function of the skin in AD.
Stratum corneum lipids are an important determinant for both water-retention function and permeability-barrier function in the stratum corneum. However, their major constituent, ceramides, have not been analyzed in detail in skin diseases such as atopic dermatitis that show defective water-retention and permeability-barrier function. In an attempt to assess the quantity of ceramides per unit mass of the stratum corneum in atopic dermatitis, stratum corneum sheet was removed from the forearm skin by stripping with cyanoacrylate resin and placed in hexane/ethanol extraction to yield stratum corneum lipids. The stratum corneum was dispersed by solubilization of cyanoacrylate resin with dimethylformamide, and after membrane filtration, the weight of the stratum corneum mass was measured. The ceramides were quantified by thin-layer chromatography and evaluated as microgram/mg stratum corneum. In the forearm skin of healthy individuals (n = 65), the total ceramide content significantly declined with increasing age. In atopic dermatitis (n = 32-35), there was a marked reduction in the amount of ceramides in the lesional forearm skin compared with those of healthy individuals of the same age. Interestingly, the non-lesional skin also exhibited a similar and significant decrease of ceramides. Among six ceramide fractions, ceramide 1 was most significantly reduced in both lesional and non-lesional skin. These findings suggest that an insufficiency of ceramides in the stratum corneum is an etiologic factor in atopic dry skin.
The mammalian stratum corneum, formerly treated as a homogeneous film, is now more properly viewed as a two-compartment system. The cornified cell is protein-enriched and lipid-depleted, lying embedded in an expanded extracellular matrix of highly nonpolar lipids. Because of its strategic location between the cornified layer, this lipid matrix is responsible for many phenomena related to the permeability barrier, as well as cohesion and desquamation. Thus, manipulation of this compartment could lead to enhanced drug delivery and improved lubrication, as well.
The factor necessary for the cure and prevention of black tongue in dogs produced on a modified Goldberger diet has been isolated from liver and identified as nicotinic acid amide. Both nicotinic acid and nicotinic acid amide are effective in curing black tongue in dogs and in maintaining dogs in a normal condition on the basal black tonque producing diet.
Serine palmitoyltransferase [palmitoyl-CoA:L-serine C-palmitoyltransferase (decarboxylating) EC 2.3.1.50] catalyzes the initial and committed step in the biosynthesis of the long-chain bases of sphingolipids. A simple assay, based upon the incorporation of [3H]serine into the chloroform-soluble product 3-ketosphinganine, has been developed and demonstrated to be valid for analyzing this enzyme in rat liver microsomes. More than 75% of the serine palmitoyltransferase of rat liver was associated with the microsomal subfraction. The dependencies of activity on the incubation time, pH, temperature, other assay components (e.g., dithiothreitol, EDTA, and pyridoxal 5'-phosphate), and the concentrations of microsomal protein, L-serine, and palmitoyl-CoA were investigated. The requirement of pyridoxal 5'-phosphate for activity was established by formation of the apoenzyme by dialysis against cysteine, and recovery of full activity upon reconstitution with the coenzyme. Activities with fatty acyl-CoA's of varying alkyl chain length were distributed nearly symmetrically around a maximum at 16 carbons (palmitoyl-CoA) for the fully saturated substrates. Less activity was obtained with the CoA thioesters of cis-unsaturated fatty acids, but trans-9-hexadecenoyl-CoA yielded essentially the same activity as palmitoyl-CoA. Hence, this enzyme is capable of initiating the synthesis of the major long-chain bases, as well as compounds that may constitute the unidentified bases reported in analyses of mammalian sphingolipids.
Using thin-layer chromatography and glass capillary gas-liquid chromatography, we have quantitated the lipids in the germinative, differentiating, and fully cornified layers in human epidermis. As previously noted in nonhuman species, we found progressive depletion of phospholipids coupled with repletion of sterols and sphingolipids during differentiation. The sphingolipids, present only in small quantities in the lower epidermis, accounted for about 20% of the lipid in the stratum corneum, and were the major repository for the long-chain fatty acids that predominate in the outer epidermis. Although the absolute quantities of sphingolipids increased in the outer epidermis, the glycolipid:ceramide ratio diminished in the stratum corneum, and glycolipids virtually disappeared in the outer stratum corneum. Squalene and n-alkanes were distributed evenly in all epidermal layers, suggesting that these hydrocarbons are not simply of environmental or pilosebaceous origin. Cholesterol sulfate, previously considered only a trace metabolite in epidermis, was found in significant quantities, with peak levels immediately beneath the stratum corneum in the stratum granulosum. These studies: 1) provide new quantitative data about human epidermal lipids; 2) implicate certain classes of lipids for specific functions of the stratum corneum; and, 3) shed light on possible product-precursor relationships of these lipids.
An improved chemiluminescence-based RNA/DNA detection procedure offering a widely applicable alternative to the conventional 32P labeling employed in molecular biology is described. Even highly sensitive applications such as Northern blot analysis of low-copy RNAs are shown to be feasible now without radioactive labeling. Improved quality of nonradioactive detection was obtained by the use of digoxigenin-labeled nucleotides in combination with dioxetane substrates which are decomposed by the hydrolysis of alkaline phosphatase. Previously existing problems involving unacceptably high background signals in nonradioactive labeling procedures were eliminated by the application of a modified RNA/DNA transfer, hybridization, and detection protocol. The data presented here delineate a system consistently superior to radioactivity and should considerably increase the usefulness of nonradioactively labeled probes detected by chemiluminescence.
The induction of programmed cell death, or apoptosis, involves activation of a signalling system, many elements of which remain unknown. The sphingomyelin pathway, initiated by hydrolysis of the phospholipid sphingomyelin in the cell membrane to generate the second messenger ceramide, is thought to mediate apoptosis in response to tumour-necrosis factor (TNF)-alpha, to Fas ligand and to X-rays. It is not known whether it plays a role in the stimulation of other forms of stress-induced apoptosis. Given that environmental stresses also stimulate a stress-activated protein kinase (SAPK/JNK), the sphingomyelin and SAPK/JNK signalling systems may be coordinated in induction of apoptosis. Here we report that ceramide initiates apoptosis through the SAPK cascade and provide evidence for a signalling mechanism that integrates cytokine- and stress-activated apoptosis.
Our analysis of epidermal lipids revealed that (glucosyl)ceramide profiles in various human skin equivalents are different from those of native tissue. The main difference is the reduced content in skin equivalents of ceramides 4-7 and especially the very low content of the most polar ceramides 6 and 7, which contain hydroxylated sphingoid base and/or fatty acid. To facilitate hydroxylation, the culture medium was supplemented with vitamins C and E. Although in vitamin E-supplemented medium lipogenesis was not affected, in vitamin C-supplemented medium the content of glucosylceramides and of ceramides 6 and 7 was markedly increased, both in the presence and absence of serum and irrespective the substrate used (inert or natural, populated or not with fibroblasts). The improvement of the lipid profile was accompanied by a marked improvement of the barrier formation as judged from extensive production of lamellar bodies, their complete extrusion at the stratum granulosum/stratum corneum interface, and the formation of multiple broad lipid lamellar structures in the intercorneocyte space. The presence of well-ordered lipid lamellar phases was confirmed by small-angle x-ray diffraction. Some differences between native and reconstructed epidermis, however, were noticed. Although the long-range lipid lamellar phase was present in both the native and the reconstructed epidermis, the short lamellar phase was present only in native tissue. It remains to be established whether these differences can be ascribed to small differences in relative amounts of individual ceramides, to differences in fatty acid profiles, or to differences in cholesterol sulfate, pH, or calcium gradients. The results indicate the key role vitamin C plays in the formation of stratum corneum barrier lipids.
Daily treatments of skin in hairless mice with concentrates of rice wine, Japanese traditional alcohol, lowered transepidermal water loss levels compared to the controls on the 3rd day after ultraviolet B (UVB) irradiation. These findings indicate that the concentrates of rice wine suppress the murine skin barrier disruption caused by UVB. Ethyl alpha-D-glucoside (alpha-ethylglucoside), one of the peculiar components in rice wine, showed the same effect, whereas beta-ethylglucoside had no effect. In order to clarify the functions of alpha-ethylglucoside on murine skin, we examined the effects of this compound on the expression of some phenotypes in human keratinocytes in vitro. As a result, alpha-ethylglucoside as well as beta-ethylglucoside enhanced cell proliferation weakly, and the formation of cornified envelopes and differentiated type keratin (K1) in keratinocytes was accelerated by alpha-ethylglucoside but not by beta-ethylglucoside. From the results, we conclude that alpha-ethylglucoside enhanced the differentiation of keratinocytes, which might be related to reduced barrier disruption by UVB.
Serine palmitoyltransferase (SPT, EC 2.3.1.50) is the key enzyme in sphingolipid biosynthesis. It catalyzes the pyridoxal-5’-phosphate-dependent condensation of L-serine and palmitoyl-CoA to 3-oxo-sphinganine. Human expressed-sequence-tag (EST) clones are similar to the two yeast genes for synthesis of long-chain bases, LCB1 and LCB2, which are believed to encode two subunits of SPT [Buede, R., Pinto, W. J., Lester, R. L. & Dickson, R. C. (1991) J. Bacteriol. 173, 4325–5332; Nagiec, M. M., Baltisberger, J. A., Wells, G. B., Lester, R. L. & Dickson, R. C. (1994) Proc. Natl Acad. Sci. USA 91, 7899–7902]. We have cloned and characterized two complete human and murine cDNA sequences named hLCB1 & mLCB1 and hLCB2 & mLCB2, respectively, similar to the yeast LCB1 and LCB2 genes.
Human embryonic kidney cells (HEK 293) transfected with murine sequences of LCB1 (mLCB1) and LCB2 (mLCB2) independently and in coexpression showed an overexpression of the transcripts on the mRNA and protein level. The enzymatic activity of cells expressing mLCB2 alone or coexpressed with mLCB1 was three times higher than the activity of untransfected HEK cells. mLCB1 expression was not required for the synthesis of 3-oxo-sphinganine in mammalian cells. Transcription/translation in vitro yielded mLCB1 (53 kDa) and mLCB2 (63 kDa). The two proteins do not contain a signal peptide nor are they glycosylated. The endogenous and overexpressed SPT activity were both sensitive to common SPT inhibitors. Labeling studies with [1-14C]palmitic acid indicated that cell lines transfected with mLCB2 preferentially use the excess sphingoid bases for glucocerebroside and galactocerebroside synthesis. Our results provide conclusive genetic and biochemical evidence that the human and murine LCB2 genes described here encode serine palmitoyltransferase. Further studies will be required to unravel the function of the LCB1 gene in mammalian cells.
Alterations in triglyceride and cholesterol metabolism often accompany inflammatory diseases and infections. We studied the effects of endotoxin (lipopolysaccharide [LPS]) and cytokines on hepatic sphingolipid synthesis, activity of serine palmitoyltransferase (SPT), the first and rate-limiting enzyme in sphingolipid synthesis, and lipoprotein sphingolipid content in Syrian hamsters. Administration of LPS induced a 2-fold increase in hepatic SPT activity. The increase in activity first occurred at 16 hours, peaked at 24 hours, and was sustained for at least 48 hours. Low doses of LPS produced maximal increases in SPT activity, with half-maximal effect seen at approximately 0.3 microg LPS/100 g body weight. LPS increased hepatic SPT mRNA levels 2-fold, suggesting that the increase in SPT activity was due to an increase in SPT mRNA. LPS treatment also produced 75% and 2.5-fold increases in hepatic sphingomyelin and ceramide synthesis, respectively. Many of the metabolic effects of LPS are mediated by cytokines. Interleukin 1 (IL-1), but not tumor necrosis factor, increased both SPT activity and mRNA levels in the liver of intact animals, whereas both IL-1 and tumor necrosis factor increased SPT mRNA levels in HepG2 cells. IL- produced a 3-fold increase in SPT mRNA in HepG2 cells, and the half-maximal dose was 2 ng/mL. IL-1 also increased the secretion of sphingolipids into the medium. Analysis of serum lipoprotein fractions demonstrated that very low density lipoprotein, intermediate density lipoprotein, and low density lipoprotein isolated from animals treated with LPS contained significantly higher amounts of ceramide, glucosylceramide, and sphingomyelin. Taken together, these results indicate that LPS and cytokines stimulate hepatic sphingolipid synthesis, which results in an altered structure of circulating lipoproteins and may promote atherogenesis.
Lipid decomposition studies in frozen fish have led to the development of a simple and rapid method for the extraction and purification of lipids from biological materials. The entire procedure can be carried out in approximately 10 minutes; it is efficient, reproducible, and free from deleterious manipulations. The wet tissue is homogenized with a mixture of chloroform and methanol in such proportions that a miscible system is formed with the water in the tissue. Dilution with chloroform and water separates the homogenate into two layers, the chloroform layer containing all the lipids and the methanolic layer containing all the non-lipids. A purified lipid extract is obtained merely by isolating the chloroform layer. The method has been applied to fish muscle and may easily be adapted to use with other tissues.Lipid decomposition studies in frozen fish have led to the development of a simple and rapid method for the extraction and purification of lipids from biological materials. The entire procedure can be carried out in approximately 10 minutes; it is efficient, reproducible, and free from deleterious manipulations. The wet tissue is homogenized with a mixture of chloroform and methanol in such proportions that a miscible system is formed with the water in the tissue. Dilution with chloroform and water separates the homogenate into two layers, the chloroform layer containing all the lipids and the methanolic layer containing all the non-lipids. A purified lipid extract is obtained merely by isolating the chloroform layer. The method has been applied to fish muscle and may easily be adapted to use with other tissues.
The extracellular matrix of stratum corneum: role of lipids in normal and pathological function
- Ml Williams
- Pm Elias
Williams ML, Elias PM. The extracellular matrix of stratum
corneum: role of lipids in normal and pathological function. CRC
Crit Rev Ther Drug Carrier Syst 1987; 3: 95±122.
Coordinate regulation of keratinocyte proliferation by ceramides and glucosylceramides
- Y Uchida
- P M Elias
- W M Holleran
Uchida Y, Elias PM, Holleran WM. Coordinate regulation of
keratinocyte proliferation by ceramides and glucosylceramides.
J Invest Dermatol 1994; 102: 594(Abstr.).