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Moisturizing effects of topical niacinamide on atopic dry skin
Abstract
Certain moisturizers can improve skin barrier function in atopic dermatitis. The effect of topical nicotinamide on atopic dry skin is unknown. We examined the effect of topical nicotinamide on atopic dry skin and compared the results with the effect of white petrolatum in a left-right comparison study.
Twenty-eight patients with atopic dermatitis, with symmetrical lesions of dry skin on both forearms, were enrolled, and were instructed to apply nicotinamide cream containing 2% nicotinamide on the left forearm and white petrolatum on the right forearm, twice daily over a 4- or 8-week treatment period. Transepidermal water loss and stratum corneum hydration were measured by instrumental devices. The amount of the stratum corneum exfoliated by tape stripping (desquamation index) was determined by an image analyzer.
Nicotinamide significantly decreased transepidermal water loss, but white petrolatum did not show any significant effect. Both nicotinamide and white petrolatum increased stratum corneum hydration, but nicotinamide was significantly more effective than white petrolatum. The desquamation index was positively correlated with stratum corneum hydration at baseline and gradually increased in the nicotinamide group, but not in the white petrolatum group.
Nicotinamide cream is a more effective moisturizer than white petrolatum on atopic dry skin, and may be used as a treatment adjunct in atopic dermatitis.
... Topical niacinamide is commonly included in cosmeceutical products for its anti-ageing, anti-blemish, skin brightening and hydration effects [1,2]. Dermal delivery of niacinamide has also been explored for alleviating skin disorders such as dermatitis and melasma, benefitting from its anti-inflammatory and skin brightening effects [13,[18][19][20][21][22]. Topical niacinamide was also used in some 3 ...
... Niacinamide is known for its ability to keep the skin barrier intact as shown in several human clinical trials witnessing a decreased transepidermal water loss (TEWL) with topical application [8,11,12,18]. This could be related to the increased activity of serine palmitoyltransferase which is responsible for sphingolipid synthesis and the synthesis of the stratum corneum (SC) lipids such as ceramides, free fatty acids and cholesterol as shown in vitro and in vivo, resulted in decreased TEWL in vivo [37]. ...
... Following this, anti-inflammatory effect (15%) gained popularity as a targeted intervention for various skin conditions including atopic dermatitis, seborrheic dermatitis, rosacea, eczema and pruritus. These studies showed reduced erythema and red blotchiness as well as less inflammatory cells infiltration [3,4,13,18,19,39,43,89,91]. Furthermore, acne, a distinctive inflammatory skin condition, was also explored, with 7% of the studies indicating a reduction in acne lesion counts, a lowered acne severity and an improved grading score [14,15,75,77]. ...
Niacinamide, an active form of vitamin B3, is recognised for its significant dermal benefits including skin brightening, anti-ageing properties and the protection of the skin barrier. Its widespread incorporation into cosmetic products, ranging from cleansers to serums, is attributed to its safety profile and proven efficacy. Recently, topical niacinamide has also been explored for other pharmaceutical applications, including skin cancers. Therefore, a fundamental understanding of the skin permeation behaviour of niacinamide becomes crucial for formulation design. Given the paucity of a comprehensive review on this aspect, we provide insights into the mechanisms of action of topically applied niacinamide and share the current strategies used to enhance its skin permeation. This review also consolidates clinical evidence of topical niacinamide for its cosmeceutical uses and as treatment for some skin disorders, including dermatitis, acne vulgaris and actinic keratosis. We also emphasise the current exploration and perspectives on the delivery designs of topical niacinamide, highlighting the potential development of formulations focused on enhancing skin permeation, particularly for clinical benefits.
... There was also a positive correlation between the severity of PPR and serum Hcy levels [27]. Studies have shown that specific B vitamins, notably B3 and B12, may influence rosacea symptoms, exhibiting both beneficial and exacerbating effects [27][28][29][30][31][32][33][34][35]. ...
... Despite their similar biological roles, they differ pharmacologically: niacin is a lipid-lowering agent known for inducing flushing [29,30]. While nicotinamide offers benefits such as improving skin barrier functions and possesses antiinflammatory properties, potentially mitigating the redness and inflammation characteristic of rosacea [31,32]. In a pilot study by Wozniacka et al., 34 rosacea patients were treated for 2 weeks with a topical gel containing 0.25% of 1-methylnicotinamide (MNA), a metabolite of nicotinamide. ...
Rosacea is a common inflammatory skin condition displaying symptoms like flushing, erythema, papules, and pustules. Oral antibiotics, despite long-term adverse effects, are often used due to topical treatment limitations, underscoring the need for cost-effective choices like dietary modifications. Our review investigates the role of vitamins and minerals in rosacea, and provides evidence-based recommendations for supplementation and topical treatment of these nutrients for rosacea. An online search was performed on PubMed, Web of Science, Science Direct, Google Scholar, and ClinicalTrials.gov from 1998 to 2023. Included studies were summarized and assessed for quality and relevance in rosacea management. Varied outcomes emerged concerning the impact of essential vitamins and minerals on rosacea treatment. Vitamin A derivatives, specifically oral isotretinoin, demonstrated significant efficacy, with a 90% reduction in lesions, complete remission in 24% of patients, and marked improvement in 57% of patients. Vitamin B3 derivatives, such as topical 1-methylnicotinamide 0.25% and NADH 1%, improved symptoms in 76.4% (26/34) and 80% of patients, respectively. Outcomes for vitamin D, vitamin C, and zinc supplementation varied across studies. However, zinc sulfate solution 5% significantly reduced acne rosacea severity for patients with 40% and 60% exhibiting a moderate or good response, respectively. Omega-3 fatty acids showed significant improvement in alleviating xerophthalmia in 64% of patients with ocular rosacea. Vitamins and minerals hold potential in managing rosacea symptoms, offering a safe and cost-effective alternative or adjunctive treatment option. Currently, there are no established recommendations regarding their supplementation for rosacea. Studies assessing serum levels of vitamins and minerals in relation to rosacea are warranted, as this avenue holds potential for future advancements in the field.
... Niacinamide (also known as nicotinamide or vitamin B3) serves as a precursor in the synthesis of the nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate, which act as coenzymes in many biochemical reactions [101,102]. When used on the skin, niacinamide helps improve several skin characteristics, including the appearance of fine lines and wrinkles, pore size, and skin texture [103]. ...
... For example, niacinamide (and its derivatives) is able to improve skin barrier functions by stimulating the de novo biosynthesis of all CERs (by 4-5 fold), FFAs (by 2.3 fold), and CHOL (by 1.5 fold) attributed to the upregulation of serine palmitoyltransferase activity-the rate-limiting enzyme in sphingolipid synthesis [101]. Moreover, niacinamide was shown to significantly decrease TEWL and effectively increase SC hydration in atopic dry skin when compared to white petrolatum [102]. In randomized, controlled, comparative studies of the SC integrity, moisturizers containing niacinamide in combination with glycerin yielded more rapid and sustained improvement in dryness and SC barrier than conventional moisturizers containing predominantly various levels of lipids (e.g., petrolatum, mineral oil, etc.) [104]. ...
This review provides an overview of the structural and functional features of key phytosphingosine-based ceramides (CERs), notably CER[EOP], CER[NP], and CER[AP], and their role in atopic skin health. Herein, we discuss how these indispensable stratum corneum (SC) lipids maintain skin barrier homeostasis and contribute to the skin’s barrier function in terms of its cohesiveness and resilience. We also consider the usefulness of CER[EOP], CER[NP], and CER[AP] in preserving skin hydration and protecting and/or repairing dry, itchy, or sensitive skin. Next, we explore how and to what extent an imbalance or inadequate amounts of CER[EOP], CER[NP], and CER[AP] contribute to the hallmark characteristics of atopic skin diseases like eczema. Furthermore, we discuss the importance of complementary SC resident lipids such as cholesterol (CHOL) and free fatty acids (FFAs), which are crucial for optimal CER function. Studies have shown that delivering topical CERs in balanced and optimal combination with CHOL and FFAs—while supporting and boosting the endogenous biosynthesis of CERs using ingredients such as niacinamide and lactic acid—helps relieve symptoms of atopic diseases to provide some measure of relief. Finally, we look at some emerging ingredients that can complement the science of CERs in healthy and diseased skin.
... 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.
... Also, the antipruritic effect of nicotinamide and its role in restoring the skin barrier, likely mediated through its interaction with AQP3, which is overexpressed in atopic dermatitis, makes this molecule mainly effective in treating this pathological condition [42,178,179]. In 2005, Soma et al. [180] conducted a study on 28 atopic patients treated with 2% nicotinamide cream for 4-8 weeks. They observed a significant reduction in the transepidermal water loss (TEWL) and an increase in stratum corneum hydration compared to untreated areas or areas treated with white petrolatum in the same patient. ...
Nicotinamide (NAM), the amide form of vitamin B3, is a precursor to essential cofactors nicotinamide adenine dinucleotide (NAD⁺) and NADPH. NAD⁺ is integral to numerous cellular processes, including metabolism regulation, ATP production, mitochondrial respiration, reactive oxygen species (ROS) management, DNA repair, cellular senescence, and aging. NAM supplementation has demonstrated efficacy in restoring cellular energy, repairing DNA damage, and inhibiting inflammation by suppressing pro-inflammatory cytokines release. Due to its natural presence in a variety of foods and its excellent safety profile—even at high doses of up to 3 g/day—NAM is extensively used in the chemoprevention of non-melanoma skin cancers and the treatment of dermatological conditions such as blistering diseases, atopic dermatitis, rosacea, and acne vulgaris. Recently, its anti-aging properties have elevated NAM’s prominence in skincare formulations. Beyond DNA repair and energy replenishment, NAM significantly impacts oxidative stress reduction, cell cycle regulation, and apoptosis modulation. Despite these multifaceted benefits, the comprehensive molecular mechanisms underlying NAM’s actions remain not fully elucidated. This review consolidates recent research to shed light on these mechanisms, emphasizing the critical role of NAM in cellular health and its therapeutic potential. By enhancing our understanding, this work underscores the importance of continued exploration into NAM’s applications, aiming to inform future clinical practices and skincare innovations.
... 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]. Moreover, it helps to protect the lipid barrier of the skin by increasing the biosynthesis of intercellular lipids [16]. ...
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.
... Interleukins like IL-4, IL-5, and IL-13 are secreted by these cells, which stimulate IgE synthesis [60]. A clinical study was undertaken for eight weeks to investigate the moisturizing impact of nicotinamide in patients with atopic dry skin and it was confirmed that surface application of niacinamide helps to sustain the skin barrier, decreasing trans-epidermal water loss (TEWL) and increasing the production of skin proteins and ceramides [62]. ...
Disruption of the skin barrier and immunity has been associated with several skin diseases, namely atopic dermatitis (AD), psoriasis, and acne. Resident and non-resident immune cells and the barrier system of the skin are integral to innate immunity. Recent advances in understanding skin microbiota have opened the scope of further understanding the various communications between these microbiota and skin immune cells. Vitamins, being one of the important micronutrients, have been reported to exert antioxidant, anti-inflammatory, and anti-microbial effects. The immunomodulatory action of vitamins can halt the progression of skin diseases, and thus, understanding the immuno-pharmacology of these vitamins, especially for skin diseases can pave the way for their therapeutic potential. At the same time, molecular and cellular markers modulated with these vitamins and their derivatives need to be explored. The present review is focused on significant vitamins (vitamins A, B3, C, D, and E) consumed as nutritional supplements to discuss the outcomes and scope of studies related to skin immunity, health, and diseases.
Graphical abstract
... Dermatology Life Quality Index (DLQI) [17] score was also used to measure the impact of the illness on the patient's quality of life and how much improvement was seen after therapy. Percentage of a possible 30 on the DLQI was used to calculate the result. ...
Cutaneous lupus erythematosus is a term for a group of autoimmune diseases that affect the skin's connective tissues. Most people with cutaneous lupus erythematosus have a type called discoid lupus erythematosus. Current treatments for DLE are hard and not always effective. They can also be very expensive, off-label, or hard to get (like antimalarials due to COVID-19 outbreaks). Nicotinamide, which is also called niacinamide, is a form of vitamin B3 that dissolves in water (niacin). Nicotinamide could be used to treat skin lesions caused by lupus because it has more than one effect. On 20 people, we did a prospective randomized clinical trial. The data that was gathered showed that topical Nicotinamide can be used to treat DLE as an addition to other treatments, with good cosmetic results and few side effects. Topical Nicotinamide at a concentration of 4% is more effective than a concentration of 2%, but it causes more irritation. We need more tests with longer-term therapy, longer follow-up periods, and bigger sample sizes.
... Niacinamide was previously demonstrated to induce enhanced exfoliation of the skin surface, showing moisturizing effects of topical nicotinamide on atopic dry skin [33]. Although niacinamide has been suggested to affect hair biology by stimulating vascular endothelial growth factor (VEGF) synthesis, testing in an in vitro VEGF synthesis assay revealed that this cannot occur across a broad dose-response range. ...
PurposeThis double-blind randomized placebo-controlled clinical study aimed to investigate the efficacy and safety of hair loss prevention shampoo with salicylic acid (0.2%), panthenol (0.2%), and niacinamide (0.1%) in alopecia patients.MethodsA total of 42 subjects completed the 24-week clinical study. A series of clinical examinations, counting of the number of hairs number on the crown, and visual and subject survey evaluations were performed at baseline and 8, 16, and 24 weeks after use to evaluate the efficacy and safety of the shampoo for preventing hair loss.ResultsThe primary endpoint was the number of hairs on the crown, which showed a significantly greater increase (17.76%) in the treatment group than in the placebo group at 24 weeks after use (p < 0.05). In the intention-to-treat population, the secondary endpoint, visual evaluation of hair loss symptoms, the crown, the line of forelock, and hair thickness also showed significantly greater increases in the treatment group than in the placebo group (p < 0.05) at 24 weeks after use. Safety evaluations confirmed no abnormal symptoms in the experimental and placebo groups.Conclusions
Therefore, this study suggests that shampoo treatment can help prevent hair loss in patients with alopecia.
... While petrolatum had no effect on skin desquamation, the niacinamide cream increased the desquamation index, which could be explained by the softening of the stratum corneum caused by the increase in hydration. However, this study lacks a vehicle control, which compromises the validity of the results [35]. Both studies showed that niacinamide topical application may improve the impaired barrier function, which has been proposed in the pathophysiology of sensitive skin. ...
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.
... PCA, which is a filaggrin breakdown product and part of the skin's natural moisturizing factor (NMF), is present as sodium PCA, the form of PCA most used in topical preparations, which helps to restore the hydration of the SC. 25 Lactic acid also forms part of the NMF, and together with nicotinamide have been shown to promote ceramide biosynthesis and thus further strengthen the skin barrier. 26,27 Similar outcomes to those observed in this study have been reported in the relatively few clinical studies examining the safety Similar results have been observed in adults and children using moisturizers containing synthetic pseudoceramides [34][35][36] or ceramide precursor lipids. 37,38 However, the nature of pseudoceramides and ceramide precursors may make them less efficacious in treating dry skin than ceramides. ...
The dysfunctional skin barrier in eczema patients may be attributed to decreased levels of ceramides in the stratum corneum. The aim of this study was to determine whether a two‐part system consisting of a ceramide‐dominant physiological lipid‐based moisturizing cream and cleanser could ameliorate the signs and symptoms of moderate eczema in adults over 28 days compared to placebo. Assessments were conducted at baseline and every 7 days thereafter. Eczema Area Severity Index (EASI) score decreased significantly across all time points in both groups compared to baseline (P < 0.0001), however, this decrease was not significant between groups at day 28 (P = 0.7804). In contrast, transepidermal water loss (TEWL) and skin hydration significantly improved over time in the active group, while it either stayed the same or worsened in the placebo group (P = 0.0342 and P < 0.0001, respectively). There was no difference in the use of mometasone furoate as rescue medication over time between groups (P = 0.1579). Dermatology Life Quality Index (DLQI) scores improved significantly in both groups (P < 0.0001), with no difference between groups (P = 0.5256). However, patient satisfaction was greater in the active compared to the placebo group for several parameters including relief of itch, dry skin, skin softness and smoothness (all P < 0.05). No patients withdrew from the study due to adverse events (AEs) and there were no serious AEs. The ceramide‐dominant moisturizing cream and cleanser safely restores skin permeability and improves the signs and symptoms of eczema in adults.
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... Nicotinamide 2% cream applied bis in die for 8 weeks demonstrated to reduce trans-epidermal water loss and was more effective than petrolatum. 28 A molecular study in vitro showed that NAM is responsible of the attenuation of aquaporin 3 overexpression induced by retinoic acid. 29 This effect of enhancing skin barrier function jointly to a molecular antiinflammatory effect explain why NAM has been proposed as adjunctive treatment in chronic dermatoses such as atopic dermatitis, 4 acne, and rosacea. ...
The incidence of skin cancer has gradually increased in the last years and exposition to ultraviolet radiation remains the main risk factor. We performed a comprehensive review on the role of nicotinamide (NAM) in the chemoprevention of skin cancers. NAM, a water‐soluble form of vitamin B3, interferes with skin carcinogenesis as it regulates immunosuppressor genes such as p53 and sirtuins and restores intracellular level of NAD+, a co‐enzyme essential for energy production. Efficacy and safety of NAM was evaluated in a phase 3 double‐blinded control‐placebo study (ONTRAC), thus demonstrating that the incidence of actinic keratoses and non‐melanoma skin cancers was lower in the nicotinamide group than in placebo group. Further studies showed the efficacy of NAM also in transplanted patients and among inhabitants living in arsenic contamination areas. Despite the quick response to NAM supplementation, its intake need to be carried on chronically as the efficacy seems to vanish rapidly.
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... Niacin can be converted from tryptophan, an essential amino acid, by the kynurenine pathway. An increased intake of tryptophan-containing foods or supplemental niacin can increase the serum level of nicotinamide; topical and oral forms of nicotinamide are effective in the treatment of dermatitis by reducing transdermal water loss [201,202]. ...
Atopic dermatitis (AD) is the leading chronic skin inflammatory disease and the initial manifestation of atopic march. Available evidence supports the notion that primary prevention early in life leads to a decreased incidence of AD, thus possibly decreasing the subsequent occurrence of atopic march. Nutritional status is essential to a proper functioning immune system and is valued for its important role in AD. Essential nutrients, which include carbohydrates, proteins, lipids, vitamins, and minerals, are transferred from the mother to the fetus through the placenta during gestation. Various nutrients, such as polyunsaturated fatty acids (PUFAs) and vitamin D, were studied in relation to maternal status and offspring allergy. However, no strong evidence indicates that a single nutrient or food in mothers’ diet significantly affects the risk of childhood AD. In the light of current evidence, mothers should not either increase nor avoid consuming these nutrients to prevent or ameliorate allergic diseases in their offspring. Each essential nutrient has an important role in fetal development, and current government recommendations suggest specific intake amounts for pregnant women. This review discusses evidence on how various nutrients, including lipids (monounsaturated fatty acids, PUFAs, saturated fatty acids, and short-chain fatty acids), carbohydrates (oligosaccharides and polysaccharides), proteins, vitamins (A, B, C, D, and E), and trace minerals (magnesium, iron, zinc, copper, selenium, and strontium) in maternal status are associated with the development of AD and their possible mechanisms.
... In addition, nicotinamide has been demonstrated to increase the skin's production of collagen and ceramides, and to stimulate keratinocyte differentiation, leading to improved barrier function and skin appearance [95], [105]. Nicotinamide cream is a more effective moisturizer than white petrolatum on atopic dry skin, and may be used as a treatment adjunct in atopic dermatitis [188]. Reported its anti-inflammatory, antioxidant and immunomodulatory properties, as well as an epithelization inducing action. ...
... The effects of NAM on skin are promptly and prominently visible. Inflammatory or autoimmune skin diseases, such as acne vulgaris (Collins et al. 1991;Shalita et al. 1995), bullous pemphigoid (Fivenson et al. 1994), and atopic dermatitis (Soma et al. 2005), have been treated or ameliorated with NAM possibly through the aforementioned anti-inflammatory effects. Wound healing in model animals was accelerated as well (Collins et al. 1991). ...
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.
... In addition, nicotinamide has been demonstrated to increase the skin's production of collagen and ceramides, and to stimulate keratinocyte differentiation, leading to improved barrier function and skin appearance [90,102]. Nicotinamide cream is a more effective moisturizer than white petrolatum on atopic dry skin, and may be used as a treatment adjunct in atopic dermatitis [159]. Ashkani et al., 2015 reported its anti-in lammatory, antioxidant, and immunomodulatory properties, as well as an epithelization inducing action. ...
... Topical nicotinamide (the active form of vitamin-B3) has been shown to improve fine lines and wrinkles, hyperpigmented spots, red blotchiness and sallowness (yellowing), as well as elasticity. In addition, nicotinamide has been demonstrated to increase the skin's production of collagen and ceramides, and to stimulate keratinocyte differentiation, leading to improved barrier function and skin appearance [95,105].Nicotinamide cream is a more effective moisturizer than white petrolatum on atopic dry skin, and may be used as a treatment adjunct in atopic dermatitis [188]. Ashkani et al., 2015 reported its antiinflammatory, antioxidant, and immunomodulatory properties, as well as an epithelization inducing action. ...
As the most voluminous organ of the body that is exposed to the outer environment, the skin suffers from both intrinsic and extrinsic aging factors. Skin aging is characterized by features such as wrinkling, loss of elasticity, laxity, and rough-textured appearance. This aging process is accompanied with phenotypic changes in cutaneous cells as well as structural and functional changes in extracellular matrix components such as collagens and elastin. With intrinsic aging, structural changes occur in the skin as a natural consequence of the biological changes over time and produce a certain number of histological, physiological, and biochemical modifications. Intrinsic aging is determined genetically (influence of gender and ethnic group), variable in function of skin site, and also influenced by hormonal changes. Visually it is characterized by fine wrinkles. By comparison, “photoaging” is the term used to describe the changes occurring in the skin, resulting from repetitive exposure to sunlight. The histological, physiological, and biochemical changes in the different layers of the skin are much more drastic. From a mechanical point of view, human skin appears as a layered composite containing the stiff thin cover layer presented by the stratum corneum, below which are the more compliant layers of viable epidermis and dermis and further below the much more compliant adjacent layer of subcutaneous white adipose tissue. Upon exposure to a strain, such a multi-layer system demonstrates structural instabilities in its stiffer layers, which in its simplest form is the wrinkling. These instabilities appear hierarchically when the mechanical strain in the skin exceeds some critical values. Their appearance is mainly dependent on the mismatch in mechanical properties between adjacent skin layers or between the skin and subcutaneous white adipose tissue, on the adhesive strength and thickness ratios between the layers, on their bending and tensile stiffness as well as on the value of the stress existing in single layers. Gradual reduction of elastic fibers in aging significantly reduces the skin’s ability to bend, prompting an up to 4-fold reduction of its stability against wrinkling, thereby explaining the role of these fibers in skin aging. Anti-aging medicine is practiced by physicians, scientists, and researchers dedicated to the belief that the process of physical aging in humans can be slowed, stopped, or even reversed through existing medical and scientific interventions. This specialty of medicine is based on the very early detection and prevention of age-related diseases. Physicians practicing anti-aging medicine seek to enhance the quality of life as well as its length, limiting the period of illness and disability toward the end of one’s life. Anti-aging medicine encompasses lifestyle changes (diet and exercise); hormone replacement therapies, as needed, determined by a physician through blood testing (DHEA, melatonin, thyroid, human growth hormone, estrogen, testosterone); antioxidants and vitamin supplements; and testing protocols that can measure not only hormone levels and blood chemistry but every metabolic factor right down to the cellular level.
... 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]. In addition, Soma and colleagues [12] showed the desquamation index increases in response to moisturization after niacinamide treatment. ...
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.
... Niacin (vitamin B3 has two potential forms that can be used in cosmeceuticals: niacinamide (nicotinamide and nicotinic acid [163]. Topical nicotinamide (the active form of vitamin-B3 has been shown to improve fine lines and wrinkles, hyperpigmented spots, red blotchiness and sallowness (yellowing, as well as elasticity. ...
Skin aging is a complex biological process influenced by a combination of endogenous or intrinsic and exogenous or extrinsic factors. Because of the fact that skin health and beauty is considered one of the principal factors representing overall “well-being” and the perception of “health” in humans, several anti-aging strategies have been developed during the last years. In contrast to thin and atrophic, finely wrinkled and dry intrinsically aged skin, premature photoaged skin typically shows a thickened epidermis, mottled discoloration, deep wrinkles, laxity, dullness and roughness. Gradual loss of skin elasticity leads to the phenomenon of sagging. Slowing of the epidermal turnover rate and cell cycle lengthening coincides with a slower wound healing and less effective desquamation in older adults. This fact is important when esthetic procedures are scheduled. On the other side, many of these features are targets to product application or procedures to accelerate the cell cycle, in the belief that a faster turnover rate will yield improvement in skin appearance and will speed wound healing. A marked loss of fibrillin-positive structures as well as a reduced content of collagen type VII (Col-7, may contribute to wrinkles by weakening the bond between dermis and epidermis of extrinsically age skin. Sun-exposed aged skin is characterized by the solar elastosis. The sparse distribution and decrease in collagen content in photoaged skin can be due to increased collagen degradation by various matrix metalloproteinases, serine, and other proteases irrespective of the same collagen production. The overall collagen content per unit area of the skin surface is known to decline approximately 1%/year. Glycosaminoglycans (GAGs are among the primary dermal skin matrix constituents assisting in binding water. In photo-aged skin, GAGs may be associated with abnormal elastotic material and thus be unable to function effectively. The total hyaluronic acid (HA level in the dermis of skin that age intrinsically remains stable; however, epidermal HA diminishes markedly. Decreased estrogen levels may play a role in skin aging in women and compounds stimulating estrogen receptors could potentially counteract some of the visible signs of aging. As people live longer, women spend a larger portion of their lives in a post-menopausal state, with a deficiency of estrogen as compared to their younger selves. Changes in diet and increasing exercise, together with a regimen of antioxidants, nutritional supplements, and growth factors, can alter how the genes express themselves. Both factors can greatly enhance the healing capability of the skin and can improve the results of cosmetic surgeries.
... In addition, nicotinamide has been demonstrated to increase the skin's production of collagen and ceramides, and to stimulate keratinocyte differentiation, leading to improved barrier function and skin appearance [95], [105]. Nicotinamide cream is a more effective moisturizer than white petrolatum on atopic dry skin, and may be used as a treatment adjunct in atopic dermatitis [188]. Ashkani et.al, 2015 reported its anti-inflammatory, antioxidant, and immunomodulatory properties, as well as an epithelization inducing action.Nicotinamide also improved tissue regeneration through the increment of fibroblast proliferation, collagen synthesis, and vascularization [189]. ...
... In addition, nicotinamide has been demonstrated to increase the skin's production of collagen and ceramides, and to stimulate keratinocyte differentiation, leading to improved barrier function and skin appearance [95], [105]. Nicotinamide cream is a more effective moisturizer than white petrolatum on atopic dry skin, and may be used as a treatment adjunct in atopic dermatitis [188]. Ashkani et.al, 2015 reported its anti-inflammatory, antioxidant, and immunomodulatory properties, as well as an epithelization inducing action.Nicotinamide also improved tissue regeneration through the increment of fibroblast proliferation, collagen synthesis, and vascularization [189]. ...
As the most voluminous organ of the body that is exposed to the outer environment, the skin suffers from both intrinsic and extrinsic aging factors. Skin aging is characterized by features such as wrinkling, loss of elasticity, laxity, and rough-textured appearance. This aging process is accompanied with phenotypic changes in cutaneous cells as well as structural and functional changes in extracellular matrix components such as collagens and elastin. With intrinsic aging, structural changes occur in the skin as a natural consequence of the biological changes over time and produce a certain number of histological, physiological, and biochemical modifications. Intrinsic aging is determined genetically (influence of gender and ethnic group), variable in function of skin site, and also influenced by hormonal changes. Visually it is characterized by fine wrinkles. By comparison, “photoaging” is the term used to describe the changes occurring in the skin, resulting from repetitive exposure to sunlight. The histological, physiological, and biochemical changes in the different layers of the skin are much more drastic. From a mechanical point of view, human skin appears as a layered composite containing the stiff thin cover layer presented by the stratum corneum, below which are the more compliant layers of viable epidermis and dermis and further below the much more compliant adjacent layer of subcutaneous white adipose tissue.
... [6] Oral NAM reduces transepidermal water loss (TEWL) by ~6%-7% as early as 3 months after commencement of doses of 1 g daily, [7] and topical 2% NAM applied twice daily over 4-8 weeks provides a more effective moisturiser as measured by a reduction in TEWL, when compared with white petroleum alone (P < 0.05). [8] Hence, NAM seems to enhance skin barrier function, which may contribute to its efficacy in rosacea and acne, and may make it an adjunctive treatment for dermatitis, [4,9] as these skin conditions demonstrate increased transepidermal water loss within the stratum corneum, when compared to healthy skin. [10][11][12] Nicotinamide has also been used topically for pigmentary disorders; NAM suppresses the transfer of melanosomes from melanocytes to keratinocytes and decreases the cutaneous pigmentation characteristic of melasma. ...
Nicotinamide is a water‐soluble vitamin B3 derivative that has many roles in medicine. This review examines the role of nicotinamide in dermatology and its actions in preventing photoageing and skin cancers in humans. Nicotinamide prevents ultraviolet radiation (UV) from reducing ATP levels and inhibiting glycolysis, thus preventing the UV radiation‐induced energy crisis. This enhances DNA repair and reduces UV‐induced suppression of immunity. Randomised controlled clinical trials have also shown that nicotinamide reduces transepidermal water loss and the development of new non‐melanoma skin cancers in high‐risk humans. This review also examines nicotinamide's safety profile.
... Since moisturizers have been corroborated to improve clinical status, restore skin barrier function, and reduce topical steroid usage in AD patients, their frequent and generous use is an essential part of treatment (15)(16)(17). Given that molecular alterations are the underlying mechanism to skin barrier defect in AD, new moisturizers with ingredients like the three SC lipids (ceramide, fatty acid, and cholesterol), niacinamide, urea, or filaggrin breakdown products are emerging to restore specific defects (18)(19)(20)(21). ...
Background: Pentasodium tetracarboxymethyl palmitoyl dipeptide-12 (PTPD-12), a newly-synthesized peptide, enhances the autophagy activity, ultimately managing inflammation.
Objective: To determine the effect of a new moisturizer containing PTPD-12 as the treatment of mild-to-moderate atopic dermatitis (AD).
Methods: In this double-blind, randomized, placebo-controlled trial, 43 patients with mild-to-moderate AD were randomly assigned to either the PTPD-12 or control groups. Evaluations were performed at baseline, week 2, and week 4, including SCORing Atopic Dermatitis (SCORAD) index score, corneometry, trans-epidermal water loss (TEWL), visual analogue scale (VAS) for pruritus, 7-point investigator’s global assessment (IGA), and collection of adverse events.
Results: The PTPD-12 group showed significant improvement with respect to SCORAD score, skin hydration, TEWL, and pruritus at weeks 2 and 4 when compared with baseline. Although the control group showed significant improvement regarding the SCORAD score and skin hydration, no significant change in TEWL or pruritus was demonstrated throughout the study. The mean changes in the SCORAD index score, skin hydration, TEWL, pruritus, and number of patients with improvement in IGA were not statistically different between the two groups.
Conclusion: The moisturizer with autophagy-stimulating property provides a good therapeutic option to mild-to-moderate atopic dermatitis by contributing to skin barrier restoration and control of inflammation.
... Specifically, PCA which is a filaggrin breakdown product and part of the skin's NMF is present as sodium PCA in Ceramide cream, the form of PCA most used in topical preparations, which helps to restore the hydration of the SC. 3 Lactic acid also forms part of the NMF, and together with nicotinamide have been shown to promote ceramide biosynthesis and thus strengthen the skin barrier. 21,22 Ceramide cream also contains ceramides 1 and 3, cholesterol and linoleic acid from safflower oil in a 3:1:1 molar ratio as it has been shown that these ingredients must be delivered in the correct ratio to have a positive effect on the integrity of the skin barrier. 4 In addition to these novel ingredients, Ceramide cream contains humectants which act similarly to NMF in corneocytes, an occludent which simulates sebum and natural lipids found on the skin, and emollients which act like the intracellualar bilayers of the SC (Table 1). ...
Background
Moisturizers are topical products designed to improve and maintain the skin barrier function and to help prevent dry skin.
Materials and methods
A new moisturizer (Ceramide cream) was formulated containing ingredients which mimic the skin’s own natural moisturizing systems. Corneometry was performed at baseline, 2, 4, 6 and 24 hours following a single application of Ceramide cream to healthy skin, and compared to three reference moisturizers available over-the-counter, and placebo. Transepidermal water loss (TEWL) was also measured following a single application of Ceramide cream compared to baseline, and its safety was assessed by repeat insult patch test, ophthalmologist and pediatric testing.
Results
A single topical application of either the Ceramide cream or the three reference moisturizers resulted in a significant increase in skin hydration over time (P<0.001). The placebo cream did not significantly increase skin hydration at any time point. At 24 hours post-application, skin hydration measured for Ceramide cream was significantly greater (P<0.05) than that measured for all three of the reference moisturizers tested. Ceramide cream was also found to significantly decrease TEWL (P<0.001) over 24 hours, and was shown to be non-sensitizing to the skin of both adults and children and non-irritating to the skin, eyes and related eye area.
Conclusion
Ceramide cream increases skin hydration and improves barrier function which may make it suitable for use on dry skin.
... 51 Niacinamide also decrease TEWL in atopic dry skin significantly better, compared to white petrolatum. 52 In randomized, controlled, comparative studies on SC integrity, niacinamide containing moisturizers application resulted in more rapid and sustained skin dryness and SC barrier improvement compared to conventional moisturizers. 53 Palmitoylethanolamide (PEA) is an endogenous lipid from fatty-acid N-acylethanolamine family. ...
Moisturizer is a major component of basic daily skin care, particularly in presence of epidermal barrier alteration and reduced epidermal water content. It is an important part of a dermatologist's strategy to maintain skin health as well as treating various dermatoses which co-exist with skin dryness, linked to impaired skin barrier function such as in atopic disorder as well as other types of dermatitis. Mastering the knowledge regarding action mechanism, application, dosage, adverse effects as well as specific clinical usage of moisturizers is must for a dermatologist, in order to support the capability to recommend their use, particularly for therapeutic purposes, in accordance with evidence-based medicine. This review is aimed to discuss the use of moisturizer both as skin health maintenance as well as a definitive or adjuvant therapy, particularly for many kinds of dermatitis.
... [8] Thus, considering various distinguishing attributes in respect of its efficacy and tolerability, the Dewderm AD cream would be a valuable addition in the treatment of mild-to-moderate AD. Most of the subjects were relieved of the symptoms and it could be mainly due to the combined action of actives present in the formulation which hydrates and prevents transepidermal water loss of the skin [10][11][12][13] , soothes and conditions the skin, thus promoting rapid healing of skin lesions in dermatitis. Overall, current study data suggest that Dewderm AD cream is clinically effective and safe in patients with mild-to-moderate AD when applied twice a day. ...
Objective: To evaluate the safety and efficacy of a formulation, Dewderm AD cream, in patients with mild-tomoderate atopic dermatitis (AD). Methods: Thirty six subjects with mild-to-moderate AD aged between 5–55 years were enrolled in the study. All 36 patients were instructed to apply Dewderm AD cream twice daily on the affected area for 60 days irrespective of their visits to the clinic. Subjects underwent evaluation of efficacy parameters, such as effect of skin surface hydration and assessment of disease severity, quality of life at the end of the treatment, and photographs were taken before and after the treatment (i.e. on day 60) to assess clinical improvement of the severity of AD. Results: Treatment with Dewderm AD cream showed statistically significant improvement in all the efficacy parameters at different time points from baseline to end of the study. A statistically significant (p < 0.05) increase in mean skin surface hydration with 54.86% improvement at visit 5 was observed when compared to baseline. SCORAD score showed 80.22% reduction in the severity of skin lesions by the end of the treatment period suggesting progressive improvement in the disease severity. Similarly, the investigator‟s global assessment (IGA) scale also showed a statistically significant reduction of 67.01% from baseline 2.69 ± 0.47 to 0.88 ± 0.40 at the end of the study (p < 0.05). The DLQI score also demonstrated a statistically significant decrease (p < 0.05) from baseline to end of the study. Additionally, photograph comparing before and after treatment showed gradual clinical improvement in severity of AD of the affected area at the end of the study in subjects who had skin lesions at baseline. No adverse events were reported during the study. Conclusion: Dewderm AD cream was very effective in treating mild-to-moderate AD by significantly reducing the disease severity without any side effects. Hence, the formulation is an effective and safe treatment option in patients with mild-to-moderate AD.
... 40 niacinamide has been shown to increase the beneficial effects of moisturizers for treating xerosis by improving the integrity of the stratum corneum 41 and increasing corneal hydration. [42][43][44] the application of niacinamide can also improve the appearance of fine lines and wrinkles, 45,46 hyperpigmentation spots, texture, red blotchiness, and sallowness. 46 In one randomized clinical trial, female subjects (n=50) with signs of facial photoaging including fine lines and wrinkles, poor texture, and hyperpigmented spots applied 5% niacinamide to half of the face and its vehicle control to the other half twice daily for 12 weeks. ...
Mature skin is prone to bruising, resulting in a condition known as actinic purpura, characterized by unsightly ecchymosis and purple patches. Similar to other skin conditions, the incidence of actinic purpura increases with advancing age and occurs with equal frequency among men and women. The unsightly appearance of actinic purpura may be a source of emotional distress among the elderly. A new product has been formulated specifically for the treatment of actinic purpura. This product contains retinol, ahydroxy acids, arnica oil, ceramides, niacinamide, and phytonadione, which effectively treat actinic purpura by improving local circulation, thickening the skin, and repairing the skin barrier. The objective of this paper is to review the beneficial properties of these ingredients and their respective roles in the treatment of actinic purpura.
... , 영양결핍 4,5) , 면역조절 불균형 6,7) , 피부장벽의 손 상 8) , 위장기능의 장애 9 ...
... The existing preclinical data show that NIC has the potential for topical application in cosmetic or pharmaceutical industry because of its barrier restoration, anti-inflammatory, and depigmenting effects. 41,42 Moreover, NIC has a therapeutic potential as an inhibitor of proinflammatory cytokines in inflammatory disease. 43 Activation of NF-κB is a very important factor in both lesional and nonlesional skin from patients with psoriasis. ...
The hybrid system based on nanoparticles (NPs) self-assembled by the conjugations of hyaluronic acid with cholesterol (HA–Chol NPs) combined with nicotinamide (NIC) for tacrolimus (FK506), ie, FK506 NPs–NIC, has been confirmed to exhibit a significant synergistic effect on FK506 permeation through and into intact skin; thus, it may be a promising approach for FK506 to effectively treat skin diseases. The aim of this study was to evaluate its potential for the treatment of psoriasis. In vitro permeation through the psoriatic skin was carried out, and the results revealed that the combination of NPs with NIC exhibited a significant synergistic effect on FK506 deposition within the psoriatic skin (3.40±0.67 μg/cm²) and penetration through the psoriatic skin (30.86±9.66 μg/cm²). The antipsoriatic activity of FK506 NPs–NIC was evaluated through the treatment for imiquimod (IMQ)-induced psoriasis. The psoriasis area and severity index (PASI) score demonstrated that FK506 HA–Chol NPs–NIC exerted the effect on ameliorating the skin lesions comparable to clobetasol propionate (a positive drug for psoriasis) and superior to commercial FK506 ointment (Protopic®), and the histological study showed that it presented a synergistic effect on antipsoriasis after FK506 incorporation into NPs combined with NIC hydrotropic system, which might ultimately increase the therapeutic effect and minimize the systemic side effects by reducing the overall dose of FK506. RAW 264.7 cell uptake presented the enhancement of drugs delivered into cells by HA–Chol NPs–NIC. The antiproliferative activity on HaCaT cells identified that FK506 HA–Chol NPs–NIC exhibited significant inhibiting effects on HaCaT proliferation. The results support that the combination of HA–Chol NPs with NIC is a promising approach for FK506 for the treatment of psoriasis.
... 23 Topical nicotinamide has also shown to be beneficial in treating atopic dermatitis, owing to its ability to reduce transepidermal water loss (TEWL), possibly as a result of ceramide production. 24 patients in the nicotinamide arm compared with the placebo arm at 12 months. 25 Another RCT suggested that topical nicotinamide and calcipotriene in combination was more effective than placebo or either constituent as monotherapy when used as a steroid-sparing topical treatment for psoriasis, with 50% of patients reporting 'clear to almost clear' outcome with combination therapy. ...
Nicotinamide (niacinamide) is the water-soluble, amide form of vitamin B3. We review the evidence underlying the use of nicotinamide for various dermatological indications, including nonmelanoma cancer prophylaxis, blistering disorders, acne vulgaris and cosmetic indications, and speculate upon its future role in dermatological practice.
... [4] In a randomised control trial, topical 2% nicotinamide applied twice a day to atopic eczema for 4 and 8 weeks significantly reduced water loss and increased stratum corneum hydration when compared with white petrolatum. [5] Orally, nicotinamide has been shown to reduce transepidermal water loss. [6] It is not fully understood how oral nicotinamide administration may alter cellular inflammation in vivo; in a limited group of healthy human participants exposed to experimental endotoxaemia it had little effect on cytokines or exhaled nitric oxide. ...
Background:
Evidence that atopic eczema partly originates in utero is increasing, with some studies linking the risk of developing the condition with aspects of maternal diet during pregnancy. Nicotinamide, a naturally occurring nutrient that is maintained through the dietary intakes of vitamin B3 and tryptophan, has been used in the treatment of some skin conditions including atopic eczema.
Objective:
To examine the relation of maternal serum concentrations of nicotinamide and related tryptophan metabolites to the risk of atopic eczema in the offspring.
Methods:
Within the UK Southampton Women Survey, infantile atopic eczema at ages 6 and 12 months was ascertained (modified UK Working Party Criteria for the Definition of Atopic Dermatitis). Maternal serum levels of kynurenine, kynurenic acid, anthranilic acid, tryptophan, nicotinamide and N1-methylnicotinamide were measured in late pregnancy by mass spectrometry (n = 497) and related to the odds ratio of infantile atopic eczema.
Results:
Maternal nicotinamide and related metabolite concentrations were not associated with offspring atopic eczema at age 6 months. Higher concentrations of nicotinamide and anthranilic acid were, however, associated with a lower risk of eczema at age 12 months (odds ratios 0.69, 95% CI 0.53-0.91/SD change, P = 0.007 and 0.63, 0.48-0.83, P = 0.001, respectively). The associations were robust to adjustment for potentially confounding variables.
Conclusion and clinical relevance:
This is the first study linking maternal serum concentrations of nicotinamide and related metabolites to the risk of atopic eczema in the offspring. The findings point to potentially modifiable maternal influences on this complex and highly prevalent condition.
Atopic dermatitis (AD) is a chronic inflammatory skin condition, characterised by dry skin, pruritus and recurrent eczematous lesions. Challenges in the management of AD include fear associated with the use of corticosteroids, compliance issues and frequent flare-ups impacting the quality of life. Moisturisers are the cornerstone of AD management. In this study, we aim to develop the evidence-based consensus recommendations regarding the role and choice of moisturisers for AD. An electronic search of the PubMed/MEDLINE and Cochrane Library was undertaken to identify the relevant articles using keywords such as ‘atopic dermatitis’, ‘eczema’, ‘moisturiser’, ‘humectant’, ‘occlusive’, ‘emollient’, ‘selection’, ‘ingredients’, ‘efficacy’, ‘safety’, ‘formulation’, ‘paediatric’, ‘adult’, ‘prevention’ and ‘guidelines’. A modified Delphi consensus methodology was used to achieve the consensus. A committee of nine dermatologists from Malaysia constituted the panel. Twenty-five questions belonging to five domains were drafted: (i) challenges impacting the regular use of moisturisers in AD; (ii) selection criteria; (iii) role of bioactive ingredients in alleviating AD symptoms; (iv) clinical effectiveness of moisturisers and (v) early initiation of moisturisers for AD prevention. Consensus was set a priori as a minimum agreement of 80%. The panel agreed that moisturisers for AD management should contain humectants, occlusives and emollients to replenish epidermal lipids, retain moisture, reduce inflammation and restore skin barrier function. Regular moisturisation decreases flare-ups and enhances the effectiveness of topical corticosteroids. The experts recommended selecting moisturisers tailored to patient needs, considering factors such as the intensity of skin dryness, site of application, formulation, active ingredients, environmental humidity, climate and cost.
Introduction
Topical therapy is the mainstay treatment of acne, and topical retinoids such as tretinoin, tazarotene, and adapalene are recommended as the first‐line therapy for mild to moderate acne. However, the cutaneous irritations may occur, and the dermocosmetics are recommended to prevent side effects of anti‐acne drugs and adhere to treatment. Thus, this study aims to compare the efficacy and tolerability of ceramides and niacinamide‐containing moisturizer (CCM) versus hydrophilic cream in combination with topical anti‐acne treatment in mild to moderate acne vulgaris.
Methods
This was an 8‐week, randomized, double‐blinded, split face study in 40 patients assigned for topical anti‐acne medications (5% benzoyl peroxide and 0.1% adapalene gel), then randomly applied CCM or hydrophilic cream. All patients were followed at week 0, 2, 4, and 8 for acne improvement, adverse reactions, biometric, and biophysical evaluation.
Results
CCM could significantly improve the non‐inflammatory, inflammatory, and total acne lesions compared with hydrophilic cream after week 8 of treatment. Interestingly, there was an improvement of global worst score, hemoglobin index, melanin index, TEWL, skin hydration, sebum production, and skin surface pH, with no statistically significant differences between the two treatments. No serious side effects from clinical application of CCM and hydrophilic cream in mild to moderate acne vulgaris patients.
Conclusion
Ceramide and niacinamide‐containing moisturizer in combination with anti‐acne medication can significantly improve acne lesions and decrease cutaneous irritations toward a satisfactory treatment outcome of mild to moderate acne vulgaris.
Atopic dermatitis is a prevalent chronic skin inflammation affecting 2.1 to 4.1% of adults globally. The complexity of its pathogenesis and the relapsing nature make it challenging to treat. Current treatments follow European Academy of Dermatology and Venerology guidelines, but advanced cases with recurring lesions lack effective therapies. To address this gap, researchers are exploring nanotechnology for targeted drug delivery. Nanoparticles offer benefits such as improved drug retention, stability, controlled release and targeted delivery through the disrupted epidermal barrier. This integrated review evaluates the current state of AD treatment and highlights the potential of novel nano-formulations as a promising approach to address the disease.
Background:
Cutaneous lupus erythematosus is an umbrella term for a group of autoimmune connective tissue disorders affecting the skin. Discoid lupus erythematosus (DLE) is the chronic condition and most common form of cutaneous lupus erythematosus.
Aims:
Current therapies of DLE are challenging and not completely satisfactory, highly expensive, off-label, or poorly available (like antimalarials due to COVID-19 outbreaks). Nicotinamide, also called niacinamide, is a water-soluble form of vitamin B3 (niacin). Its multiple effects let us think that nicotinamide could be a therapy for lupus-associated skin lesions.
Methods:
We performed a prospective randomized double-blind clinical trial on 60 subjects diagnosed with Discoid lupus erythematosus using topical Nicotinamide 2% and 4% preparations in form of cream and gel on skin and scalp lesions. Control group was included using only cream/gel base as placebo control.
Results:
Obtained data showed that topical Nicotinamide can be used for the treatment of DLE as adjuvant to other treatment regimens with good cosmetic results and minimal side effects. Topical 4% Nicotinamide is superior to 2% preparation in response but associated with a higher incidence of irritation.
Conclusion:
Topical Nicotinamide can be used for the treatment of DLE as an adjuvant to other treatment regimens with good cosmetic results and minimal side effects. Further trials with long-term therapy, follow-up period, and bigger sample sizes are required.
As new biophysical methods become available to the skin researcher it is important to understand the type of information that they are capable of measuring, and how it relates to consumer perception of topical moisturizing products. The aim of the work presented here was to understand what dry skin imaging can reveal about the skin and subject feedback from the use of a topical moisturizing product and how it relates to the consumer usage experience of a topical product. Images from a dry skin camera—the Visioscan® VC 20plus—during 3 weeks in vivo usage of a topical moisturizing product were analyzed. Subject feedback regarding their skin condition was also collected. Strong statistical improvements (p < 0.05) were observed for a wide range of skin parameters derived from the Visioscan® VC 20plus. Skin scaliness and smoothness and parameters associated with skin health and appearance (surface, energy, contrast, homogeneity) improved as a result of topical product usage. Subjects reported their skin to feel less dry, to be smoother, and more supple and to look and feel healthier after product usage. The length of time until they felt the need to re-apply the product increased during the study
This is the English version of guidelines for the management of asteatosis 2021 in Japan. Asteatosis is a synonym of xerosis found in a wide range of diseases that induce dry skin through impaired functions of either water retention of the stratum corneum or skin covering with acid mantle. Patients with asteatosis may be accompanied by pruritus. Moisturizers are the first-line treatment for asteatosis and their adequate use must be recommended. The main purpose of the present guidelines is to define skin symptoms requiring treatment with moisturizers for medical use in patients with asteatosis. If the deterioration of marked scaling or scratch marks is predicted, therapeutic intervention with moisturizers for medical use should be considered even in the absence of pruritus. Regarding six important points requiring decision-making in clinical practice (clinical questions), we evaluated the balance between the benefits and harm of medical interventions in reference to previous reports of clinical research, and presented the recommendation grades and evidence levels to optimize the patient outcome by medical interventions.
Background
Nicotinamide (vitamin B3) is a metabolite of tryptophan and dietary precursor of enzymes involved in many regulatory processes, which may influence fetal immune development.
Objective
We examined whether maternal plasma concentrations of nicotinamide, tryptophan or nine related tryptophan metabolites during pregnancy were associated with risk of development of infant eczema, wheeze, rhinitis or allergic sensitization.
Methods
In the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, we analysed the associations between maternal plasma levels of nicotinamide, tryptophan and tryptophan metabolites at 26-28 weeks gestation and allergic outcomes collected through interviewer-administered questionnaires at multiple timepoints and skin prick testing to egg, milk, peanut and mites at age 18 months. Multivariate analysis was undertaken adjusting for all metabolites measured, and separately adjusting for relevant demographic and environmental exposures. Analyses were also adjusted for multiple comparisons using the false discovery method.
Results
Tryptophan metabolites were evaluated in 976/1247 (78%) women enrolled in GUSTO. In multivariate analysis including all metabolites, maternal plasma 3-hydrokynurenine was associated with increased allergic sensitization at 18 months (AdjRR 2.6, 95% CI 1.3-5.2 for highest quartile) but the association with nicotinamide was not significant (AdjRR 1.8, 95% CI 0.9-3.6). In analysis adjusting for other exposures, both 3-hydrokynurenine and nicotinamide were associated with increased allergic sensitization (AdjRR 2.0, 95% CI 1.1-3.6 for both metabolites). High maternal plasma nicotinamide was associated with increased infant eczema diagnosis by 6 and 12 months, which was not significant when adjusting for all metabolites measured, but was significant when adjusting for relevant environmental and demographic exposures. Other metabolites measured were not associated with allergic sensitisation or eczema, and maternal tryptophan metabolites were not associated with offspring rhinitis and wheeze.
Conclusions and Clinical Relevance
Maternal tryptophan metabolism during pregnancy may influence the development of allergic sensitization and eczema in infants.
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.
Purpose: Type 2 diabetes mellitus (DM) induces various dermatological conditions that can affect patient quality of life, including increased susceptibility to skin infections and dry skin. While the mechanisms that underlie the causes of dry skin in type 1 DM have been widely studied, how type 2 DM elicits similar effects is unclear. The purpose of this study was therefore to evaluate skin barrier and hydration function using a KK-Ay/TaJcl mouse model of type 2 DM.
Materials and methods: KK-Ay/TaJcl and control mice were housed separately for 4 weeks and then body weight, water intake, urine production, and blood glucose levels were measured. Skin barrier function was estimated by assessing transepidermal water loss (TEWL) and hydration levels of the stratum corneum. The expression levels of various skin biochemical factors were also examined by western blot, including type 1 collagen, mast cell tryptase, hyaluronic acid binding protein (HABP), and fibroblast protein S100A4.
Results: Compared to control mice, there was a marked increase in body weight, water intake, urine production, and blood glucose levels in the KK-Ay/TaJcl mice over the length of the experiment. Hydration levels in the stratum corneum were lower in KK-Ay/TaJcl mice compared to control mice, although TEWL was not significantly different between groups. We also found that hyaluronic acid binding protein expression was higher in KK-Ay/TaJcl mice, although other biochemical factors were the same.
Conclusions: These findings suggest that hyaluronic acid associates with the dry skin caused by type 2 DM. This contributes to understanding this phenomenon and may lead to better treatment options for patients in the future.
The role of dietary factors is an important and controversial topic in the pathogenesis of atopic dermatitis (AD). Despite the preponderance of consumer products utilizing oral micronutrients supplementation for relief AD symptoms, less attention has been paid on the utility of topical micronutrients, specifically for individuals with AD. We review evidence on topical formulations of vitamins (A, B, C, D, and E) and trace minerals (magnesium, manganese, zinc, and iodine) for treatment of AD. While topical B, C, and E formulations appear to provide some benefit to AD individuals, topical vitamin A has no utility, and topical vitamin D may exacerbate symptoms. Magnesium, zinc, and iodine all appear to improve AD through anti‐inflammatory and anti‐microbial effects, though future studies must evaluate their use as monotherapy. The exposition of the effects that topical micronutrients have on AD offers an adjuvant treatment modality for this common inflammatory dermatosis.
The transdermal delivery of cosmetic ingredients is often resisted by the outer layer of the skin, which can prevent diffusion of cosmetic ingredients through the skin. Ethosomes, lipid carriers composed mainly of phospholipids and ethanol, are one of the methods used to overcome the limitation of the skin barrier for cosmetic ingredients. We prepared ethosomes containing Rhodamine B (Rh-B) and investigated the correlation between the synthesis conditions of ethosomes and ethosome size and entrapment efficiency of Rh-B within the ethosome. Based on the correlation results, we examined the effect of ethosome size and entrapment efficiency of Rh-B within the ethosome on skin permeation of Rh-B. The skin permeability of Rh-B increased as ethosome size decreased and entrapment efficiency of Rh-B increased. Finally, the Rh-B or niacinamide loaded within ethosomes showed significantly higher skin permeation. The results indicated that using ethosomes can improve the skin permeability of niacinamide, and the same effect can be expected for other cosmetic ingredients.
Background
Topical application of tacrolimus (FK506) was effective in the treatment of atopic dermatitis (AD); however, adverse effects frequently occurred with the increase of FK506 dose during long–term treatment.
Objective
The objective of this project was to develop a hybrid skin targeting system encapsulating FK506 based on nicotinamide (NIC) and chitosan nanoparticles (CS–NPs), ie, FK506–NIC–CS–NPs, which took advantages of both of NIC and CS–NPs to obtain the synergetic effects of percutaneous delivery and treatment efficacy enhancement along with dose reduction.
Methods
The formulation of FK506–NIC–CS–NPs was optimized and characterized. In vitro and in vivo skin permeation studies were performed. AD–like skin lesions were constructed with BALB/c mice by 1–chloro–2, 4–dinitrobenzene (DNCB)–induced, and FK506–NIC–CS–NPs containing different dose of FK506 were topically administered to treat AD–like skin lesions in comparison with Protopic.
Results
NIC was found to significantly increase the FK506 EE to 92.2% by CS–NPs. In comparison with commercial FK506 ointment (Protopic), in vitro and in vivo skin permeation studies demonstrated that NIC–CS–NPs system significantly enhanced FK506 permeation through and into the skin, and deposited more FK506 into the skin. The treatment efficacy on clinical symptoms, histological analysis, and molecular biology of the AD–mice demonstrated that NIC–CS–NPs with ~1/3 dose of FK506 of Protopic was superior to that of Protopic, and NIC–CS–NPs vehicle exhibited the adjuvant therapy and moderate anti–AD effects.
Conclusion
The system of NIC–CS–NPs enhances the permeability of FK506, plays an adjuvant role in anti-AD, reduces the dose of FK506 in treating AD, and is therefore a promising nanoscale system of FK506 for the effective treatment of AD.
Die Haut als Ich-bezogenes Organ des menschlichen Körpers dient auch der Kommunikation mit dem Gegenüber und wurde seit jeher bewusst in ihrer Erscheinung modifiziert. So reichen die Ursprünge kosmetischer Behandlungen durch Externa (auch zur Faltenbehandlung) viele Jahrtausende zurück. Schon im alten Ägypten spielten kosmetische Anwendungen, nicht nur bei Frauen, sondern auch bei Männern, eine große Rolle.
Normale Haut ist definiert als Zustand ohne sichtbare Läsionen und ohne Empfindungen des Unwohlseins [4]. Dieser Zustand resultiert aus einem Gleichgewicht diverser physiologischer Parameter einschließlich Feuchtigkeitsgehalt, Talgproduktion, Verhornung und Abschuppung. Trockene Haut (Xerosis cutis) ist ein Hautzustand, der angeboren und erworben sein kann. Dieser Hautzustand, der, wie Ergebnisse einer eigenen Untersuchung bestätigen, sehr häufig ist, kann so geringfügig ausgeprägt sein, dass er nur eine kosmetische Beeinträchtigung darstellt, kann aber bei maximaler Ausprägung auch zu einer schweren Dermatose führen. Jedoch kommt in der Dermatokosmetik gerade der milden Xerosis cutis eine wichtige Bedeutung zu, auch was die Beratung hinsichtlich einer hautzustandsgerechten Hautreinigung und Hautpflege anbelangt.
Dissolving microneedles are transdermal delivery systems designed to mechanically penetrate the skin and fully dissolve in the skin in a minimally invasive manner. In this study, the skin permeability of compounds encapsulated in microneedles was controlled by changing the composition of microneedle materials. Sodium hyaluronate (SH) and carboxymethyl cellulose (CMC) were chosen as structural materials and amylopectin was used to increase the mechanical strength of microneedles. To determine the effect of microneedle composition on skin permeability, microneedle properties such as mechanical strength and solubility were investigated according to various compositions of SH and CMC. When the CMC fraction in the needle increased, the mechanical strength of the microneedle increased, leading to high skin permeability of rhodamine B, a model compound. Using microneedles, significantly higher skin permeability of niacinamide was also obtained. These results indicate that the microneedles developed in this study improved the skin permeability of compounds loaded in the needle, and the skin permeability could be tuned by changing the composition of microneedle materials.
Delivery of sufficient amounts of cosmetic ingredients through the skin is a big challenge in the cosmetic industry, since the stratum corneum, the outer layer of the skin, acts as a barrier against external substances. One of the methods to solve this problem is using microneedles. In this study, a laser-writing process is described for fabricating a polydimethylsiloxane mold for microneedles, which is a very simple and efficient method compared to the conventional photolithography technique. Using this polydimethylsiloxane mold, it was possible to fabricate a dissolving sodium hyaluronate microneedle array with consistent shapes and sizes. Amylopectin was used to tailor the properties of the microneedles, such as mechanical strength and solubility. When amylopectin content in the needle increased, the mechanical strength of the needle increased but the dissolution rate of the microneedles decreased. Using the microneedle array, significant enhancement in the skin permeability of niacinamide and the anti-oxidant activity of ascorbic acid after crossing the skin was observed. These results indicate that the microneedle array developed in this study has the potential to be used in cosmetics by being combined with conventional cosmetic patches.
Objective: To observe the efficacy of plateau lip care balm on plateau cheilitis. Methods: A randomized and parallel-controlled trial was performed in the garrison of Tibet in areas at different altitudes. The subjects were treated with plateau lip care balm (n = 177) or Chlortetracycline eye ointment (control, n = 173). The median lesion healing and the healing rate of surface were recorded day by day in the two groups during the trial period. The drying area, scaling area, article chapped number and incidence of adverse reactions were evaluated in the subjects. Results: After treatment with plateau lip care balm, the daily healing rate was between 0.00%-51.38% and the median daily healing rate was 9.00 days, which were significantly different from those in the control group (P <0.01). The changes in VAS of satisfaction scoring before and after treatment were determined by analysis of covariance, and the difference between the two groups was statistically significant (P < 0.05). Conclusion: The efficacy of plateau lip care balm on plateau cheilitis is confirmed ; it is significantly better than that of aureomycin eye ointment, providing a reliable method for the treatment of plateau cheilitis.
Tape-stripping of the skin is a useful method for removing the stratum corneum and obtaining more information about the function of this skill layer as the main barrier for skin penetration. The amount of stratum corneum removed is of relevance in establishing the concentration profile of chemicals within the stratum corneum after topical application. Weighing is the preferred method for measuring the amount stripped, but because it is often subject to artifacts, alternative methods are sought. We present a simple, colorimetric method for determining the amount stratum corneum removed by sequential adhesive-tape-stripping of human skin in vivo. The method is based on quantification of the sodium hydroxide soluble protein fraction using a commercially available protein assay similar to the Lowry assay. The method is shown to be an accurate and reproducible alternative to weighing, also demonstrating uniform removal of stratum corneum layers following the very initial strips.
It is currently fashionable to consider atopic dermatitis (AD), like other inflammatory dermatoses, as immunologic in pathogenesis ("inside-outside" hypothesis). Accordingly, topical glucocorticoids and other immunosuppressive agents are mainstays of therapy, but the risk of toxicity from these agents is not insignificant, particularly in children. Alternatively, because stratum corneum (SC) permeability barrier function is also abnormal in AD, it has been hypothesized that the barrier abnormality could drive disease activity. Yet commonly used emollients and moisturizers do not correct the SC ceramide deficiency, the putative cause of the barrier abnormality.
We assessed the efficacy of a newly developed, ceramide-dominant, physiologic lipid-based emollient, when substituted for currently used moisturizers, in 24 children who were also receiving standard therapy for stubborn-to-recalcitrant AD.
All subjects continued prior therapy (eg, topical tacrolimus or corticosteroids), only substituting the barrier repair emollient for their prior moisturizer. Follow-up evaluations, which included severity scoring of atopic dermatitis (SCORAD) values and several biophysical measures of SC function, were performed every 3 weeks for 20 to 21 weeks.
SCORAD values improved significantly in 22 of 24 patients by 3 weeks, with further progressive improvement in all patients between 6 and 20 or 21 weeks. Transepidermal water loss levels (TEWL), which were elevated over involved and uninvolved areas at entry, decreased in parallel with SCORAD scores and continued to decline even after SCORAD scores plateaued. Both SC integrity (cohesion) and hydration also improved slowly but significantly during therapy. Finally, the ultrastructure of the SC, treated with ceramide-dominant emollient, revealed extracellular lamellar membranes, which were largely absent in baseline SC samples.
These studies suggest that (1) a ceramide-dominant, barrier repair emollient represents a safe, useful adjunct to the treatment of childhood AD and (2) TEWL is at least as sensitive an indicator of fluctuations in AD disease activity as are SCORAD values. These studies support the outside-inside hypothesis as a component of pathogenesis in AD and other inflammatory dermatoses that are accompanied by a barrier abnormality.
Emollients can increase the water content in the stratum corneum by delivery of their water to the skin, and by occlusion. These two mechanisms were studied using three preparations with different concentrations of lipids. The products were applied to the skin and then removed by cleaning the surface after 5 and 40 min. The increase in skin water loss following removal of product residue was considered as a release of excess water in the skin. Exposure of the skin to pure petrolatum for 5 min gave no increase in the water loss from the skin surface following removal of the product residue. A lipid rich cream (66% lipids) gave a significant increase, but the highest increase was found after removal of an ordinary cream (27% lipids). Release of water from the skin indicates that water in the creams had previously been absorbed into the skin. The occluding properties of the products were determined after 40 min of exposure. Petrolatum reduced the water loss by approximately 50% and the other products by 16%. The occlusion caused an increase of water in the skin, which resulted in a release of water following removal of the products. The release was related to the reduction of water loss. Thus petrolatum gave a higher release of water than the other emollients.
The biophysical properties of non-eczematous skin at three locations in atopics and non-atopics were characterized using non-invasive physical methods. Skin friction was measured with a newly developed sliding friction instrument, the degree of hydration with a capacitance meter (Corneometer CM 820), and the transepidermal water loss (TEWL) was determined using an Evaporimeter EP1. The areas examined (dorsum of the hand, volar forearm and lower back) showed lower values of friction and capacitance in the atopic patients than did corresponding sites in the normal controls. In most areas a significant correlation between friction and capacitance was found. The TEWL was increased in atopic skin, but TEWL seems to correlate neither to friction nor to capacitance.
Ointments (e.g., petrolatum) are thought to be occlusive, thereby blocking transcutaneous water loss and trapping water under the skin's surface. If this premise is correct, then petrolatum should delay barrier recovery after barrier perturbation, as shown previously in occluded murine skin.
We reexamined the assumption that Vaseline Petroleum Jelly (VPJ) is occlusive, ascertaining both its site and mechanism of action.
Barrier recovery was measured in VPJ-treated versus untreated sites after acetone-induced barrier disruption in human volunteers. Moreover, VPJ was localized within the stratum corneum (SC) with tracers and ruthenium tetroxide staining, which allowed visualization of the depth of VPJ penetration and its relation to intercellular membrane structures.
VPJ accelerated, rather than impeded, barrier recovery. Moreover, VPJ was present within the interstices at all levels of the SC, where it replaced intercellular bilayers.
VPJ neither forms nor acts like an epicutaneous impermeable membrane; instead, it permeates throughout the SC interstices, allowing normal barrier recovery despite its occlusive properties.
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.
To obtain data on the function of the epidermal barrier in patients with atopic dermatitis (AD) the transepidermal water loss (TEWL) was studied. Measurements were made on three body locations in two clinically well defined groups of patients with AD and in a control group. The TEWL was found to be increased both in dry non-eczematous skin and in clinically normal skin in patients with AD. The TEWL was highest in patients with dry skin. The result of the study may indicate a primary defect in the epidermal barrier: the stratum corneum.
The dry looking skin seen in many patients with atopic dermatitis reflects a defect in the epidermal barrier, the stratum corneum, as demonstrated by an increased transepidermal water loss (TEWL) and a decreased ability of the stratum corneum to bind water. The absolute amount of water within the stratum corneum is of importance both for barrier properties and for the clinical appearance of the skin. This water content was measured with a new instrument, the Corneometer CM 420, which takes advantage of the high dielectric constant of water. Forty patients with atopic dermatitis were studied--20 with dry skin and 20 with clinically normal skin on non-eczematous areas. The stratum corneum in dry skin was found to have a lower content of water than that in the clinically normal skin (p less than 0.01). Clinically normal skin in patients with atopic dermatitis did not differ significantly from normal control skin. An experiment was performed in vitro in an attempt to correlate the values obtained with the Corneometer to the absolute amount of water within the corneum.
An open study of high dose nicotinamide in the treatment of 15 patients with necrobiosis lipoidica is reported. Of 13 patients who remained on treatment for more than 1 month, eight improved. Improvement took the form of a decrease in pain and soreness, a decrease in erythema and the healing of ulcers if present, although the skin did not return completely to normal in any patient. There were no significant side-effects, particularly with respect to diabetic control, an important finding as lesions tended to relapse if treatment was stopped.
Necrobiosis lipoidica is a granulomatous condition which usually arises on the shins, although lesions have been reported to occur on other parts of the body. It is usually found in association with diabetes (although only a small proportion of diabetic patients develop this lesion) and the pathogenesis is unknown. However, abnormalities in dermal collagen,1 vascular supply of the skin,2 and immunological responses3, 4 have been demonstrated.
The lesions, which comprise yellow, telangiectatic, atrophic plaques with a variable degree of erythema usually only present a cosmetic problem, although in some cases they can be painful or itchy, or may ulcerate. Available treatment, including topical steroids, systemic aspirin and dipyridamole, and surgical excision and grafting tend to be unsatisfactory. Following the report of the use of high dose nicotinamide in granuloma annulare,5 we report the results of an open study of high dose nicotinamide in patients with necrobiosis lipoidica and present an illustrative case history.
Active dermatitis causes a disturbance in skin barrier function. This can be evaluated by the measurement of transepidermal water loss (TEWL) and percutaneous absorption of hydrocortisone.
The study objective was to evaluate changes in skin barrier function during treatment of atopic dermatitis.
Nine patients with widespread atopic dermatitis were studied longitudinally by measuring the severity of the dermatitis and TEWL at intervals of 1 to 3 days. Percutaneous absorption of hydrocortisone was measured at entry and during treatment.
At entry, both TEWL and percutaneous absorption of hydrocortisone were elevated. Four to six days later, a significant decline was observed in both variables, indicating rapid improvement in skin barrier function. Individual changes in TEWL correlated with the changes in the systemic absorption of hydrocortisone.
TEWL reflects changes in the systemic absorption of topical hydrocortisone during treatment of atopic dermatitis.
During recent years several highly developed non-invasive methods for evaluation of skin physiology and pathology have been introduced. Against this background, the present studies were undertaken with the primary aim of assessing the effects of various skin care products on some properties of the skin. Skin topography was measured by profilometry on skin replicas, friction with a newly developed friction instrument, capacitance with a Corneometer, and barrier function both with an Evaporimeter to assess transepidermal water loss (TEWL) and by application of an irritant followed by measurement of the resulting irritative reaction. Initially some of the techniques were used to further characterize the differences between dry atopic skin and normal skin. Dry skin exhibits increased values of roughness parameters and a reduced number of topographical peaks. TEWL is increased, indicating impaired barrier function. The friction and capacitance are lower and correlate significantly to each other, whereas TEWL does not appear to relate to either of these parameters. The use of a scrub cream removes the outermost part of the stratum corneum, resulting in a smoother skin. Application of moisturizers modifies the frictional response of the skin. The friction instrument gave results comparable to those of panelists trained in sensory evaluation. The study suggests that measurement of skin friction can be used to predict the degree of liking of moisturizers. Furthermore, moisturizers increase the skin hydration. They provide water directly to the skin from their water phase. Skin hydration also increases with increased degree of occlusion, as measured as a decrease in TEWL. Moisturizers may also alter the diffusional resistance of the stratum corneum and reduce the skin susceptibility to the surfactant sodium lauryl sulphate (SLS). Lipids in moisturizers may influence already developed SLS-induced irritation. A significantly lower degree of irritation was found in areas treated with canola oil and its sterol-enriched fraction than in an area treated with water. These findings emphasize that skin care products do not only form an inert, epicutaneous layer, but that they may penetrate and influence the structure and function of the skin.
Systemic and topical antimicrobials are effective in the treatment of inflammatory acne vulgaris; however, widespread use of these agents is becoming increasingly associated with the emergence of resistant pathogens raising concerns about microorganism resistance and highlighting the need for alternative nonantimicrobial agents for the treatment of acne. Nicotinamide gel provides potent antiinflammatory activity without the risk of inducing bacterial resistance.
In our double-blind investigation, the safety and efficacy of topically applied 4% nicotinamide gel was compared to 1% clindamycin gel for the treatment of moderate inflammatory acne vulgaris. Seventy-six patients were randomly assigned to apply either 4% nicotinamide gel (n = 38) or 1% clindamycin gel (n = 38) twice daily for 8 weeks. Efficacy was evaluated at 4 and 8 weeks using a Physician's Global Evaluation, Acne Lesion Counts, and an Acne Severity Rating.
After 8 weeks, both treatments produced comparable (P = 0.19) beneficial results in the Physician's Global Evaluation of Inflammatory Acne; 82% of the patients treated with nicotinamide gel and 68% treated with clindamycin gel were improved. Both treatments produced statistically similar reductions in acne lesions (papules/pustules; -60%, nicotinamide vs. -43%, clindamycin, P = 0.168), and acne severity (-52% nicotinamide group vs. -38% clindamycin group, P = 0.161).
These data demonstrate that 4% nicotinamide gel is of comparable efficacy to 1% clindamycin gel in the treatment of acne vulgaris. Because topical clindamycin, like other antimicrobials, is associated with emergence of resistant microorganisms, nicotinamide gel is a desirable alternative treatment for acne vulgaris.
In order to obtain objective data on skin functions in subjects with atopic dermatitis (AD), according to the different phases of the disease, we evaluated the skin of children with AD instrumentally and compared it to that of healthy subjects of the same age group. One hundred patients, aged 3 to 12, and 21 healthy children were studied by means of measurements of pH, capacitance and transepidermal water loss (TEWL) at 8 different skin sites. At the moment of the investigation 55 children out of 100 presented skin lesions on at least one of the assessed skin areas, whereas 45 had been free from eczema for at least 1 month. Considering all skin sites together, significant differences were found between mean values of pH, capacitance and TEWL of eczematous skin, both in respect to those referring to apparently healthy skin in the same patients and in respect to the skin of control subjects. Moreover, TEWL, pH and capacitance values referring to uninvolved skin of AD patients significantly differed from those of healthy subjects. Finally, when values referring to patients with skin lesions and to patients without lesions were separately considered, significant differences concerning the parameters of uninvolved skin were observed. These data show that, in subjects with AD, skin functions undergo fluctuations according to the phase of the disease and support the hypothesis that the presence of active eczema determines an impairment of the barrier of uninvolved skin, even at sites far from active lesions.
Clinical grading of dry skin syndromes (xerosis) is beset by many variables which limit its reliability. Removing scales onto adhesive coated discs (D-Squames®) has provided a means for objective measurement of xerotic slates. Using image analysis we have modified the basic procedure to assure greater accuracy and reproducibility. The distribution of grey values on the discs was determined, from which a single value of the degree of scaling was calculated. We term this the sealing index.
To induce xerosis, the lower legs of 12 women, aged 26-64, were washed daily for 10 days with soap. After washing, one side received a moisturizing lotion, the other served as an untreated control. At specified intervals, scaling was graded clinically, electrical conductance was measured and D-Squames® were obtained.
On the moisturizer-treated legs there was a significant decrease in dryness grades and scaling indices at all time points. Conductance was significantly increased on days 8 and 11. The untreated washed legs showed no changes in clinical grades, although conductance significantly decreased and the scaling indices increased in the last stage of the study.
D-Squame® analysis unequivocally revealed the beneficial effect of a moisturizer on soap-induced xerosis and the expected increase in scaliness without treatment.
Ultraviolet (UV) B irradiation leads to a potent immunosuppression of the capacity to reject syngeneic, antigenic tumors. If this immunosuppression is critical for the development of most skin tumors, then its prevention should result in prevention of photocarcinogenesis. We previously showed a correlation between the inhibition of photoimmunosuppression and prevention of photocarcinogenesis by dl-alpha-tocopherol, tannic acid, or alpha-difluoromethylornithine. The current study was designed to determine whether topical nicotinamide, the active form of vitamin B-3, or niacin, prevents immunosuppression and skin cancer in UV-irradiated mice. In a passive transfer assay for immunosuppression, splenocytes from UV-irradiated mice enhanced the growth of antigenic tumor challenges in recipient mice. Treatment of the UV-irradiated mice with 40 mumol of nicotinamide twice weekly starting two weeks before UV irradiation and throughout the experiment prevented this immunosuppression. UVB irradiation consisted of five weekly 30-minute exposures to banks of six FS40 Westinghouse fluorescent sunlamps. Mice received approximately 6.2 x 10(5) J/m2 in the passive transfer assays and 1.09 x 10(6) J/m2 in the photocarcinogenesis studies. Application of nicotinamide to UV-irradiated mice reduced skin tumor incidence from 75% to 42.5% (p = 0.016, Cox proportional hazards analysis). Thus topical nicotinamide prevented the immunosuppression and skin tumor induction by UVB irradiation.
Patients with atopic skin show a defective barrier function both in rough and in clinically normal skin, with an increasing risk of developing contact dermatitis. Moisturizing creams are often used in the treatment of dry skin. The purpose of this study was to investigate the influence of treatment with a urea-containing moisturizer on the barrier properties of atopic skin. Fifteen patients with atopic dermatitis treated one of their forearms twice daily for 20 days with a moisturizing cream. Skin capacitance and transepidermal water loss (TEWL) were measured at the start of the study and after 10 and 20 days. On day 21 the skin was exposed to sodium lauryl sulphate (SLS) and on day 22 the irritant reaction was measured non-invasively. Skin capacitance was significantly increased by the treatment, indicating increased skin hydration. The water barrier function, as reflected by TEWL values, tended to improve (P = 0.07), and the skin susceptibility to SLS was significantly reduced, as measured by TEWL and superficial skin blood flow (P < 0.05). Thus, it seems that certain moisturizers could improve skin barrier function in atopics and reduce skin susceptibility to irritants. The mechanism and the clinical relevance need further investigation.
Although it has been well established that the dry skin often seen in patients with atopic dermatitis shows a deranged barrier function, there is no unanimity of opinion as to whether the barrier in normal-appearing skin of patients with the disease is deranged or not. Hence, it remains unclear whether individuals with atopic dermatitis constitution have an intrinsic derangement of skin barrier function or not. To settle this problem, in the present study we examined transepidermal water loss and stratum corneum water content in normal appearing skin of the upper back of 16 patients with completely healed atopic dermatitis who had been free from skin symptoms for 5 years or more, 30 patients with active atopic dermatitis, and 39 healthy subjects. The transepidermal water loss values and the stratum corneum water content values in normal-appearing skin of the completely healed patients were not different from the values in normal controls. These findings indicate that skin barrier function is not disturbed in patients with completely healed atopic dermatitis.
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.
The cutaneous permeability barrier is localized to the stratum corneum interstices and is mediated by lamellar bilayers enriched in cholesterol, free fatty acids and ceramides. Topically applied lipids may interfere with the skin barrier function and formulations containing "skin-identical lipids" have been suggested to facilitate normalization of damaged skin. The aim of the present study was to compare the ability of "skin-identical lipids" in a petrolatum-rich cream base and pure petrolatum to facilitate barrier repair in detergent- and tape-stripped-perturbed human skin. Barrier recovery and inflammation were instrumentally monitored for 14 days as transepidermal water loss and skin blood flow, using an Evaporimeter and a laser Doppler flowmeter, respectively. Treatment with the 2 different products gave no indication that "skin-identical lipids" in a cream base are more efficient than pure petrolatum at promoting normalization in either of the 2 experimentally perturbed areas. This finding may support the hypothesis that different types of skin abnormality should be treated according to the underlying damage.
Cutaneous hyperpigmentation occurs in multiple conditions. In addition, many Asian women desire a lighter skin colour. Thus, there is a need for the development of skin lightening agents. Niacinamide is a possible candidate.
To investigate the effects of niacinamide on melanogenesis in vitro and on facial hyperpigmentation and skin colour in vivo in Japanese women.
Melanin production was measured in a purified mushroom tyrosinase assay, cultured melanocytes, a keratinocyte/melanocyte coculture model, and a pigmented reconstructed epidermis (PREP) model. The clinical trials included 18 subjects with hyperpigmentation who used 5% niacinamide moisturizer and vehicle moisturizer in a paired design, and 120 subjects with facial tanning who were assigned to two of three treatments: vehicle, sunscreen and 2% niacinamide + sunscreen. Changes in facial hyperpigmentation and skin colour were objectively quantified by computer analysis and visual grading of high-resolution digital images of the face.
Niacinamide had no effect on the catalytic activity of mushroom tyrosinase or on melanogenesis in cultured melanocytes. However, niacinamide gave 35-68% inhibition of melanosome transfer in the coculture model and reduced cutaneous pigmentation in the PREP model. In the clinical studies, niacinamide significantly decreased hyperpigmentation and increased skin lightness compared with vehicle alone after 4 weeks of use.
The data suggest niacinamide is an effective skin lightening compound that works by inhibiting melanosome transfer from melanocytes to keratinocytes.