ArticleLiterature Review

Niacinamide - Mechanisms of Action and Its Topical Use in Dermatology

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

Abstract

Niacinamide, an amide of vitamin B3 (niacin), is a hydrophilic endogenous substance. Its effects after epicutaneous application have long been described in the literature. Given a sufficient bioavailability, niacinamide has antipruritic, antimicrobial, vasoactive, photo-protective, sebostatic and lightening effects depending on its concentration. Within a complex metabolic system niacinamide controls the NFκB-mediated transcription of signalling molecules by inhibiting the nuclear poly (ADP-ribose) polymerase-1 (PARP-1). Niacinamide is a well-tolerated and safe substance often used in cosmetics. Clinical data for its therapeutic use in various dermatoses can increasingly be found in the literature. Although the existing data are not sufficient for a scientifically founded evaluation, it can be stated that the use of niacinamide in galenic preparations for epicutaneous application offers most interesting prospects. © 2014 S. Karger AG, Basel.

No full-text available

Request Full-text Paper PDF

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

... • Dexpanthenol contributes to barrier function recovery in dry conditions and enhances epidermal differentiation 24,34 • Argan oil, shea butter, and squalene are physiological lipids, which act as substitutes for lost natural skin lipids in the outer layers of the stratum corneum 24,30 • Glycerin acts as a humectant to restore water content and barrier function 24,29 • Niacinamide is an anti-pruritic/soothing agent 35,36 • Isopropyl isostearate is a non-physiological lipid, which contributes to normalization of the altered lipid organization/composition in the stratum corneum 24,37 Bepanthen SensiDaily (Bepanthen) ...
... 26,56 In the studies identified, there was notable variability in the designs, populations, and types of data reported; thus, direct cross-study comparisons are not recommended. Standardization of reporting in emollient plus research may allow • Niacinamide is an anti-pruritic/soothing agent 35,36 • Sterols help to restore the skin barrier function 14,16 • Licorice extract reduces inflammation 13 • Laureth-9-polydocanol reduces itching 20 • Xylitol and galacto-oligosaccharide are prebiotics that inhibit the growth of harmful bacteria and promote the growth of beneficial bacteria such as Staphylococcus epidermidis, to maintain the natural skin microbiome [17][18][19] EpiCeram (Primus Pharmaceuticals) ...
... • • Niacinamide is an anti-pruritic/soothing agent 35,36 • Shea butter fills the cracks between desquamating corneocytes and smoothens the skin 11 • Mannose acts as a carbon source to promote the growth of members of Xanthomonadaceae family 46 • Vitreoscilla filiformis biomass normalizes skin microbiota 46 Restoraderm (Galderma Cetaphil) Ceramides, filaggrin breakdown products (arginine and pyrrolidone carboxylic acid), niacinamide [47][48][49] • Ceramides and filaggrin breakdown products help replenish components necessary for skin barrier function 48 • Niacinamide is an anti-pruritic/soothing agent 35,36 XeraCalm A.D. DovePress stronger conclusions to be drawn regarding efficacy. It should also be noted that this narrative review did not employ systematic review methodology; the publications listed may not represent an exhaustive list of available studies. ...
Article
Full-text available
Emollients are the mainstay maintenance treatment for atopic dermatitis (AD). A novel generation of emollients, 'emollients plus', containing active, non-medicated substances, has softened the distinction between emollients and topical drugs. A literature search for selected key words was performed using PubMed. Additional papers were identified based on author expertise. Whilst the inclusion of five components of an ideal emollient has been proposed, no such consensus exists for emollients plus and they can vary markedly in their composition and modes of action for AD treatment. This could have a profound effect on their clinical efficacy. The efficacy of emollients plus in restoring and maintaining skin barrier function has been demonstrated on multiple levels, with evidence reported for their effects on the physical and biochemical, microbial, immunological, and neurosensory barriers. When selecting an appropriate AD treatment approach, the safety profiles of the available topical therapies must be carefully considered. There are several proposed treatment approaches for AD, including preventive, proactive, intermittent, and synergistic approaches. Emollients plus may be effective not only as maintenance therapy for AD, but also when used synergistically with anti-inflammatory pharmacological therapies.
... Lipikar Baume AP+M is a hydrating moisturizer, primarily consisting of water, niacinamide, shea butter and aquae posae filiformis. Niacinamide, an amide of vitamin B 3 (niacin), has anti-pruretic, anti-inflammatory, depigmenting and photo-protective properties [43,44]. In addition, it helps to protect the lipid barrier of the skin by increasing the biosynthesis of intercellular lipids [43,44]. ...
... Niacinamide, an amide of vitamin B 3 (niacin), has anti-pruretic, anti-inflammatory, depigmenting and photo-protective properties [43,44]. In addition, it helps to protect the lipid barrier of the skin by increasing the biosynthesis of intercellular lipids [43,44]. Shea butter contains lipids that are similar to those of the skin, thereby supporting the skin's natural lipid layers [45]. ...
... Paradoxically, this increase in epidermal water content can lead to dehydration and worsening of the scar [40]. However it is possible that moisturizers such as Lipikar Baume AP+M which lack adequate occlusion, provide improved protection against dehydration over time due to stimulation of barrier repair by inducing lipid synthesis in combination with an excellent dermatological tolerance [43,44,66]. ...
Article
Background The mainstay of non-invasive scar management, consists of pressure therapy with customized pressure garments often combined with inlays, hydration by means of silicones and/or moisturizers as well as UV protection. It is generally accepted that scar dehydration resulting from impaired barrier function of the stratum corneum and expressed by raised trans epidermal water loss (TEWL) values, can lead to increased fibroblast activity and thereby hypertrophic scar formation. However, there is no consensus on exactly what optimal scar hydration is nor on barrier function repair: by means of silicone sheets, liquid silicone gels or moisturizers. Occlusive silicone sheets almost completely prevent TEWL and have been shown to be effective. Nevertheless, many important disadvantages due to excessive occlusion such as difficulties in applying the sheets exceeding 10–12 h, pruritus, irritation, and maceration of the skin are limiting factors for its use. To avoid these complications and to facilitate the application, liquid silicone gels were developed. Despite a reduced occlusion, various studies have shown that the effects are comparable to these of the silicone sheets. However, major limiting factors for general use are the long drying time, the shiny aspect after application, and the high cost especially when used for larger scars. Based on excellent clinical results after using three specific moisturizers for scar treatment in our patients, we wanted to investigate whether these moisturizers induce comparable occlusion and hydration compared to both each other and the widely recognized liquid silicone gels. We wanted to provide a more scientific basis for the kind of moisturizers that can be used as a full-fledged and cost-effective alternative to silicone gel. Methods A total of 36 healthy volunteers participated in this study. Increased TEWL was created by inducing superficial abrasions by rigorous (20x) skin stripping with Corneofix® adhesive tape in squares of 4 cm². Three moisturizers and a fluid silicone gel were tested: DermaCress, Alhydran, Lipikar and BAP Scar Care silicone gel respectively. TEWL reducing capacities and both absolute (AAH) and cumulative (CAAH) absolute added hydration were assessed using a Tewameter® TM300 and a Corneometer® CM825 at different time points for up to 4 h post-application. Results There was an immediate TEWL increase in all the zones that underwent superficial abrasions by stripping. Controls remained stable over time, relative to the ambient condition. The mean percentage reduction (MPR) in TEWL kept increasing over time with Alhydran and DermaCress, reaching a maximum effect 4 h post-application. Silicone gel reached maximal MPR almost immediately post-application and only declined thereafter. The silicone gel never reached the minimal MPR of Alhydran or DermaCress. Hydration capacity assessed through CAAH as measured by the Corneometer was significantly less with silicone gel compared to the moisturizers. Compared to silicone gel Lipikar provided similar occlusion and the improvement in hydration was highly significant 4 h post-application. Conclusion Based on the results of both our previous research and this study it is clearly demonstrated that the occlusive and hydrative effect of fluid silicone gel is inferior to the moisturizers used in our center. Lipikar hydrates well but is less suitable for scar treatment due to the lack of occlusion. A well-balanced occlusion and hydration, in this study only provided by Alhydran and DermaCress, suggests that moisturizers can be used as a scar hydration therapy that replaces silicone products, is more cost-effective and has a more patient-friendly application.
... Nowadays, niacinamide has extensive usage in the treatment of melasma and hyperpigmentation. Niacinamide has sufficient bioavailability and is used in cosmetics in different concentrations [7,8]. ...
... In the current study, the decrease in erythema level of volunteers' skin was due to the presence of niacinamide/ferulic acid. Both the compounds have the capacity to inhibit the production and regulation of proinflammatory cytokines (IL-1, IL-6, IL-10, and IL-12) [8] and inflammatory mediators (COX-2 and PGE2) which are involved in the photoinduced erythema [1,17]. The decrease in melanin level by MNF was due to the presence of these compounds which have the tendency to inhibit melanogenesis by inhibiting melanocytic proliferation and tyrosinase activity which is a key enzyme for melanin synthesis [9]. ...
Article
Full-text available
Objective: Multiple emulsions have the ability to incorporate both lipophilic and hydrophilic actives in the same preparation and facilitate permeation of active ingredients through skin. The current study was aimed at formulating niacinamide/ferulic acid-loaded stable multiple emulsion (MNF) and its in vitro/in vivo characterization as a cosmeceutical product. Methods: Both the compounds were evaluated for their radical scavenging potential by the DPPH method and FTIR analysis. Then, placebo and active formulations were prepared using a double emulsification method and were investigated for stability testing (changes in color, odor, and liquefaction on centrifugation, pH, and globule size) for a period of three months. Afterwards, MNF was investigated for in vitro sun protection factor, rheological studies, entrapment efficiency, zeta potential, zeta size, and ex vivo permeation. Moreover, after ensuring the hypoallergenicity and safety, it was also checked for its cosmeceutical effects on human skin using noninvasive biophysical probes in comparison with placebo. Results: Results demonstrated that MNF showed a non-Newtonian behavior rheologically and both MNF and placebo were stable at different storage conditions. Entrapment efficiency, zeta potential, and zeta size were 93.3%, -5.88 mV, and 0.173 μm, respectively. Moreover, melanin, sebum, and skin erythema were significantly reduced while skin elasticity and hydration were improved. Conclusion: It is evident that niacinamide and ferulic acid can be successfully incorporated in a stable multiple emulsion which has potent cosmeceutical effects on human skin.
... This finding can be attributed to niacinamide, which is an ingredient of DFC, DFC-SPF, and NFC. Niacinamide, an amide of vitamin B 3 , penetrates the SC effectively and increases the biosynthesis of natural SC lipids [12,13,35], apart from its antipruritic/soothing properties [13]. The effect of niacinamide on natural SC lipid content may have contributed to the increased facial moisturization mediated by DFC, DFC-SPF, and NFC. ...
... This finding can be attributed to niacinamide, which is an ingredient of DFC, DFC-SPF, and NFC. Niacinamide, an amide of vitamin B 3 , penetrates the SC effectively and increases the biosynthesis of natural SC lipids [12,13,35], apart from its antipruritic/soothing properties [13]. The effect of niacinamide on natural SC lipid content may have contributed to the increased facial moisturization mediated by DFC, DFC-SPF, and NFC. ...
Article
Full-text available
Three novel face creams containing dexpanthenol with different lipid contents were developed for dry skin sufferers: a day face cream (DFC), a day face cream with sun protection (DFC-SPF), and a night face cream (NFC). Three identically designed studies (N = 42–44 each) were conducted with healthy adults of three ethnicities (African, Asian, Caucasian) with dry/sensitive skin. Effects on stratum corneum (SC) hydration, SC lipid content, and skin elasticity were quantified by established noninvasive methods during the 4-week studies. After single and repeated once-daily applications of the face creams, facial hydration significantly increased from baseline. On day 28, the mean increments in skin hydration amounted to 27%, 26%, and 27% (p < 0.0001 each) for DFC, DFC-SPF, and NFC, respectively. Favorable effects of DFC, DFC-SPF, and NFC on facial moisturization were observed in all three ethnic groups. The enhancements in SC hydration were not paralleled by improvements in skin elasticity parameters but lipid analyses showed significant increases in SC cholesterol, SC free fatty acid, and/or SC ceramide levels. All three face creams were well tolerated and achieved a high product satisfaction and acceptability by study participants. Our findings support the once-daily use of the face creams in adults of different ethnicities with dry and sensitive skin.
... 3 Topical niacinamide, or nicotinamide, is an amide of vitamin B3 (niacin) with anti-in ammatory e ects that reduces facial sebum production and also induces skin lightening. 4 It is widely used in cosmetic preparations and is considered safe up to 5%. 5 This study compared a combination of 2.5% benzoyl peroxide plus 5% niacinamide with 2.5% benzoyl peroxide plus cream base for the treatment of acne vulgaris. We aimed to evaluate whether 5% niacinamide was an e ective drug for better treatment results in mild to moderate acne vulgaris. ...
... It has many pharmacological properties related to the dermatologic eld,including an antiin ammatory e ect. 4 Niacinamide reduces in ammation in many pathways. The nuclear factor kappa light-chain-enhancer of activated B-cells (NF-κB) pathway is essential for the expression of adhesion molecules, chemokines, in ammatory cytokines, and pro-in ammatory mediators. ...
Article
ABSTRACT: Background. The combination of benzoyl peroxide and a new topical therapy, such as topical niacinamide, reduces facial sebum production and also has a skin-lightening effect. This combined treatment might lead to improved efficacy in the treatment of facial acne vulgaris while also promoting the resolution of postacne erythema and postinflammatory hyperpigmentation. Objective. The primary objective was to evaluate and compare the clinical efficacy of topical 2.5% benzoyl peroxide plus 5% niacinamide and 2.5% benzoyl peroxide with cream base for mild to moderate facial acne vulgaris. Secondary objectives were to evaluate and compare clinical efficacy regarding postinflammatory hyperpigmentation, postacne erythema, reduction of facial sebum production, and side effects. Methods. Patients with mild to moderate facial acne vulgaris and aged 18 to 40 years were enrolled. Treatment was randomly assigned to the left or right side of the face for 12 weeks. Both inflammatory and noninflammatory acne lesions were counted by a physician, and the postinflammatory hyperpigmentation score and postacne erythema score were calculated using an Antera 3D® camera (Miravex, Dublin, Ireland). Sebum casual level was measured using a Sebumeter® (Courage+Khazaka Electronic, Köln, Germany) every two weeks. Physician improvement score, patient satisfaction index, and side effects were assessed by evaluation forms every two weeks. Results. At Week 12, the niacinamide group (5% niacinamide+2.5% benzoyl peroxide) showed significant reduction in both the acne lesion count and sebum casual levels from baseline (p=0.000 and p=0.001, respectively). The reduction in noninflammatory lesion count in the niacinamide group was better than that in the cream base group (2.5% benzoyl peroxide+cream base), with a statistically significant difference (p=0.004). However, the reduction in inflammatory lesions was not significantly different between the two groups. The sebum casual level in the niacinamide group was reduced faster than that in the cream base group. The postacne erythema score was reduced from baseline in both groups, with no statistically significant difference within or between the two groups. The postinflammatory hyperpigmentation score showed increases in both groups above the baseline, with a statistically significant difference in the cream base group (p=0.000) but no such difference in the niacinamide group (p=0.58). There was no statistically significant difference between the two groups. Furthermore, no statistically significant differences were found between the two groups at every follow-up visit in terms of physician improvement scale, patient satisfaction index, or side effects. Conclusion. The combination of 2.5% benzoyl peroxide and 5% niacinamide is more effective than 2.5% benzoyl peroxide alone for mild to moderate facial acne vulgaris. Keywords: Niacinamide, benzoyl peroxide, acne vulgaris
... Niacinamide (Nam; aka nicotinamide, vitamin B 3 ) has been used for decades in cosmetic and pharmaceutical products for the treatment of acne, photoageing attributes and barrier integrity improvement. [6][7][8] It has been reported that Nam can protect cells from oxidative stress, UV-induced immunosuppression and metabolic disruption. [9][10][11] Mechanistically, it has become apparent that Nam can have a significant impact on numerous processes associated with skin homeostasis and ageing. ...
... 3 Over the past few decades, Nam has become an important molecule in cosmetic and pharmaceutical products for the treatment of acne, skin photoageing attributes, and barrier integrity improvement. [6][7][8] Nam has been reported to protect cells from oxidative stress, metabolic disruption, and inflammation. 9,10 Relevant to protecting from environmental insults, Nam has also been shown to inhibit acute and chronic damaging effects of UV exposure on skin. ...
Article
Background Macromolecules in skin cells are damaged when exposed to environmental stressors, leading to disrupted cellular function and homeostasis. While epidermal turnover can eliminate some of this damage, autophagy can rapidly remove these defective components. Niacinamide (Nam) is known to induce autophagy and optimizing formulations to maximize this response could provide improved homeostasis in stressed skin. Objective To determine (i) whether Nam can induce autophagy related 5 (ATG5), an autophagy marker, in human keratinocytes and (ii) whether optimized low pH Nam formulations can enhance the response in 3D skin models. Methods Human keratinocytes treated with Nam were evaluated for autophagosome accumulation and induction of ATG5 by gene expression, immunoblotting and immune‐fluorescence microscopy. 3D skin equivalents were topically treated with Nam formulations at pH 5.8 and 3.8. Gene expression profiling and immunoblot analysis of ATG5 were performed. Results Nam treatment of keratinocytes led to an accumulation of autophagosomes with a maximal signal at 48 h. Gene expression of ATG5 was induced by Nam, and immunoblots stained for ATG5 showed a significant increase after 6 h of treatment. Gene expression profiling of 3D epidermal skin equivalents treated with Nam at pH 3.8 showed stronger induction of autophagy‐related genes, including ATG5, compared with pH 5.8 formulas. Enrichment for gene ontology terms on autophagy showed an increased linkage with Nam formulas at pH 3.8. Conclusions We found that Nam induces autophagosome accumulation and ATG5 levels in keratinocytes. We also discovered that a Nam formulation at pH 3.8 can further increase levels of ATG5 in 3D skin models when compared to Nam at pH 5.8. These data support that Nam can induce autophagy in keratinocytes and formulations at pH 3.8 can enhance the impact. We hypothesize that optimized formulations at pH 3.8 can improve skin ageing appearance via autophagy induction.
... Niacinamide (nicotinamide) is the amide in vivo product of nicotinic acid (niacin, vitamin B3) and is also a precursor of the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NAD-P). Pharmacological applications of niacinamide exert antipruritic, antimicrobial, and vasoactive effects 33 and are protective in various inflammatory cutaneous conditions, 34−36 though it is not known if these occur at concentrations generated endogenously. 33 Niacinamide has not been used to treat burn injury clinically, though it enhances wound healing upon systemic administration 37 and corrects postburn nicotinamide coenzyme system imbalances 38 experimentally. ...
... Pharmacological applications of niacinamide exert antipruritic, antimicrobial, and vasoactive effects 33 and are protective in various inflammatory cutaneous conditions, 34−36 though it is not known if these occur at concentrations generated endogenously. 33 Niacinamide has not been used to treat burn injury clinically, though it enhances wound healing upon systemic administration 37 and corrects postburn nicotinamide coenzyme system imbalances 38 experimentally. The present work is therefore the first to report the elevation of niacinamide in burn injury. ...
Article
Full-text available
Burn injury can be a devastating traumatic injury, with long-term personal and social implications for the patient. The many complex local and disseminating pathological processes underlying burn injury’s clinical challenges are orchestrated from the site of injury and develop over time, yet few studies of the molecular basis of these mechanisms specifically explore the local signalling environment. Those that do are typically destructive in nature and preclude the collection of longitudinal temporal data. Burn injury therefore exemplifies a superficial temporally-dynamic pathology for which experimental sampling typically prioritizes either specificity to the local burn site or continuous collection from circulation. Here, we present an exploratory approach to the targeted elucidation of complex, local, acutely temporally-dynamic interstitia through its application to burn injury. Subcutaneous microdialysis is coupled with ultra performance liquid chromatography – mass spectrometry (UPLC-MS) analysis, permitting the application of high throughput metabolomic profiling to samples collected both continuously and specifically from the burn site. We demonstrate this workflow’s high yield of burn-altered metabolites including the complete structural elucidation of niacinamide and uric acid, two compounds potentially involved in the pathology of burn injury. Further understanding the metabolic changes induced by burn injury will help to guide therapeutic intervention in the future. This approach is equally applicable to the analysis of other tissues and pathological conditions, so may further improve our understanding of the metabolic changes underlying a wide variety of pathological processes.
... It affects the rehydration of the skin, enhancement of re-epithelialization of the epidermis, and proliferation of fibrowww.jcosmetmed.org blasts [21]. ...
... Disodium adenosine phosphate was also developed as an active ingredient to suppress melanin accumulation by promoting epidermal turnover [75]. Furthermore, vitamin B3, niacinamide, has been reported to block the transfer of melanosomes at the surfaces of epidermal cells [76][77][78][79]. Some of these skin-lightening ingredients are also used in Korea and China. ...
Article
Full-text available
Japanese pharmaceutical cosmetics, often referred to as quasi-drugs, contain skin-lightening active ingredients formulated to prevent sun-induced pigment spots and freckles. Their mechanisms of action include suppressing melanin production in melanocytes and promoting epidermal growth to eliminate melanin more rapidly. For example, arbutin and rucinol are representative skin-lightening active ingredients that inhibit melanin production, and disodium adenosine monophosphate and dexpanthenol are skin-lightening active ingredients that inhibit melanin accumulation in the epidermis. In contrast, oral administration of vitamin C and tranexamic acid in pharmaceutical products can lighten freckles and melasma, and these products are more effective than quasi-drugs. On the basis of their clinical effectiveness, skin-lightening active ingredients can be divided into four categories according to their effectiveness and adverse effects. This review discusses academic research and development regarding skin-lightening ingredients in Japan.
... Flushing is a possible side effect of niacinamide-containing products. The offender ingredient is niacin, a form of vitamin B3 that can show up as a contaminant if raw material quality is not monitored properly [16,75]. ...
Article
Full-text available
Moisturizers are one of the most widely used preparations in cosmetics and have been extensively used to soften the skin for consumers. Moisturizers work effectively in combating dry skin which may cause pain, tightness, itch, stinging, and/or tingling. The aim of this review is to evaluate published studies on the history, ingredients, preparation processes, characteristics, uses, and applications of moisturizers. Moisturizers bridge the gap between medicine and consumer goods by being used to make the skin more beautiful and healthy. In the future, in moisturizer therapy, the capacity to adapt specific agents to specific dermatological demands will be crucial. Cosmetically, moisturizers make the skin smooth by the mechanism of increasing the water content in the stratum corneum, hence exerting its most vital action, which is moisturizing action and maintaining a normal skin pH.
... Physiological lipids penetrate the SC and support the normalization of the affected lipid composition/organization [1,16]. Glycerin and niacinamide (nicotinamide) act as humectant and antipruritic/soothing agent, respectively [17][18][19]. Dexpanthenol stimulates protein/lipid synthesis and supports epidermal regeneration by enhancing epidermal differentiation. In addition, it compensates for reduced hydration by retaining/increasing molecular mobility/fluidity of the SC lipid lamellae and proteins [1,20,21]. ...
Article
Full-text available
A new dexpanthenol-containing hand cream (ND-HC) was developed for people with dry, sensitive, and/or environmentally stressed hands. To explore the performance and acceptability of ND-HC, we conducted a randomized, intraindividual comparison study in 40 healthy adult subjects with sensitive and very dry skin on the hands. Instrumental measurements determined the effects on stratum corneum (SC) hydration and transepidermal water loss (TEWL) after single and/or 4 weeks’ use of ND-HC. Single and continued at least four times daily applications of ND-HC to very dry skin of the hand for 4 weeks triggered significant increases in SC hydration. On day 29, the mean change in skin capacitance from baseline was significantly greater when ND-HC was applied to the test area compared with the untreated area on the contralateral hand (12.41 vs. 4.46 a.u.; p < 0.001). Upon use of ND-HC over 4 weeks, mean TEWL decreased significantly (bilateral difference: −1.8 vs. 1.0 g/m2/h; p = 0.003), indicating an improvement in SC barrier function. A reduction in dry hand symptoms was observed over the study course. ND-HC was well tolerated and achieved a high level of acceptance and satisfaction. Our findings suggest that ND-HC complies with the required features of a state-of-the-art hand cream.
... Niacinamide inhibits these mediators providing sebostatic and anti-inflammatory activity. [42] Niacinamide is a cofactor of endogenous enzymes like NAD and NADP. It stimulates epidermal production of ceramides, proteins, keratin, involucrin, filaggrin, collagen, several mRNA transcriptional factors, and extracellular matrix components like elastin, fibronectin-1, fibulin, and lysyl oxidase. ...
Article
Cosmeceuticals are cosmetic products with biologically active ingredients purporting to have drug-like benefits. Cosmeceuticals are one of the fastest-growing segments of the personal care industry as their use has drastically increased over the years. Vitamins being one of the popular ingredients in cosmeceuticals have numerous skin benefits. Vitamins are organic micronutrients essential for the proper functioning of the body. The popular vitamins used in cosmetics are vitamin A, vitamin B 3, vitamin C, vitamin E, and vitamin K. These vitamins play an important role in treating skin conditions like acne, hyperpigmentation, and photoaging, protecting from UV, deactivating free radicals, and improving skin moisture retention levels of the skin. This review article emphasizes on the novel formulation of the vitamins-based cosmeceuticals. The novel carriers system has gained importance in cosmetic delivery due to its advantages such as enhanced skin penetration, sustained and controlled drug release profile, maintenance of the concentration within the therapeutic range, with greater safety and targeted delivery of active to the desired tissues. © 2021 Journal of Reports in Pharmaceutical Sciences Published by Wolters Kluwer-Medknow.
... [22][23] The biological activities of NIA also include antimicrobial, photo-protection, lighting, anti-inflammation and anti-pruritus. 25 Therefore, it could be considered as an effective ingredient for skin radiance. ...
Article
ntroduction: Skin appearance plays as an important moderator in human daily social interactions so everyday we see new and innovative solutions to fight the signs of aging. One of the important parameters of skin appearance is skin complexion radiance as it could Reflect the general health, emotional State, hormonal status, nutrition, fatigue, age or environmental factors such as smoking, drinking, seasons, etc. Objective: The objective of the study was to evaluate the effect of the daily application of a bi-phasic serum during 8 weeks on the skin radiance and skin aging parameters of healthy women with dull complexion. Subjects and method: 30 healthy female volunteers of 35 to 60 years old were enrolled in the study. The activated product (aquaserum and liposerum) were applied to the face, twice a day for 8 weeks. The evaluation was performed on T0 and T8 weeks by measuring the skin radiance using clinical scoring C.L.B.T.TM and Glossymeter® GL200, Crow’s feet wrinkles by Bazin visual perioral scale, skin elasticity by Cutometer® SM575, and also the subject’s self-assessment. Results: All 30 subjects finished the study without any serious adverse events. The results revealed a significant improvement in all C.L.B.T.TM indicators presenting skin radiance through an increase of Luminosity (29%), Transparency (28%), Brightness (27%) (p=0.001) while a decrease of Pink Red (38%), Olive (31%), Beige (30%), Light Pink (21%) parameters (p<0.001).For skin relief, statistical analyses revealed a significant decrease of wrinkles’ depth evaluated by clinical scoring (9%, p=0.003). For the elasticity, an improvement which tends to be significant (0.462±0.098 at T0 and 0.506±0.111 at T8 weeks; p=0.06) for the Ur/Ue parameter, was observed.After 8 weeks of topical application of Perfectil® Twin-Serum, the subjects significantly found that their skin is less dull (p=0.002), less red (p=0.002), with less spots (p=0.044), less sagging (p=0.002) and less wrinkles (p=0.002). Conclusion: The results observed in this trial show that 8 weeks of Perfectil® Twin Serum use provide beneficial effect on skin radiance and skin surface relief (wrinkle depth). The action of the bi-phasic product may have a positive effect on the immediate penetration of the product which should be evaluated through the further studies. Furthermore, the ingredients seem to restore the skin lipidic layer, which explains its protective effect during winter time.
... When 10% nicotinamide was applied to the skin, human subjects did not feel stinging sensation or flushing, and irritation did not appear in a single-use primary irritation test or a cumulative irritation test for 21 days with 5% product [158]. Thus, nicotinamide is well tolerated by the skin at the normally used concentrations (<5%) [159]. Nevertheless, the skin reaction to nicotinamide can vary depending on the skin condition of each individual; thus, it is necessary to consult a doctor if severe side effects exist. ...
Article
Full-text available
Vitamin B3 (nicotinic acid, niacin) deficiency causes the systemic disease pellagra, which leads to dermatitis, diarrhea, dementia, and possibly death depending on its severity and duration. Vitamin B3 is used in the synthesis of the NAD+ family of coenzymes, contributing to cellular energy metabolism and defense systems. Although nicotinamide (niacinamide) is primarily used as a nutritional supplement for vitamin B3, its pharmaceutical and cosmeceutical uses have been extensively explored. In this review, we discuss the biological activities and cosmeceutical properties of nicotinamide in consideration of its metabolic pathways. Supplementation of nicotinamide restores cellular NAD+ pool and mitochondrial energetics, attenuates oxidative stress and inflammatory response, enhances extracellular matrix and skin barrier, and inhibits the pigmentation process in the skin. Topical treatment of nicotinamide, alone or in combination with other active ingredients, reduces the progression of skin aging and hyperpigmentation in clinical trials. Topically applied nicotinamide is well tolerated by the skin. Currently, there is no convincing evidence that nicotinamide has specific molecular targets for controlling skin aging and pigmentation. This substance is presumed to contribute to maintaining skin homeostasis by regulating the redox status of cells along with various metabolites produced from it. Thus, it is suggested that nicotinamide will be useful as a cosmeceutical ingredient to attenuate skin aging and hyperpigmentation, especially in the elderly or patients with reduced NAD+ pool in the skin due to internal or external stressors.
... Any changes in PAR-2 activity can enhance or inhibit melanosome transfer and affect pigmentation [6]. Nicotinamide can block the transfer of melanosomes to keratinocytes by inhibiting the cell-signaling pathway PAR-2 and other keratinocyte factors to decrease melanogenesis [7,8]. ...
Article
Full-text available
Background: Topical nicotinamide (NAM) can reduce excessive melanin deposition in cell culture, by reversibly blocking the transfer of melanosomes from melanocytes to the adjacent keratinocytes. Thus, it has been increasingly used as a whitening agent. Objective: To assess the efficacy and safety of topical nicotinamide used for the treatment of melasma and hyperpigmentation. Methods: An electronic search for topical nicotinamide was carried out on Pubmed and Medline databases to identify studies that addressed this topic as a whitening agent. And to review the primary and secondary outcomes. Results: A significant decrease in hyperpigmentation and increased skin lightness was found with the use of topical nicotinamide, compared with the vehicle In two small sample size clinical studies. Combined regimens including nicotinamide and other ingredients offer more synergistic effects than monotherapy. Conclusion: Due to the lack of sufficient evidence, the use of nicotinamide for melasma remains controversial. Extended randomized, double-blind, placebo-controlled trials with long-term follow-up periods are needed to assess the efficacy of nicotinamide as a whitening agent.
... neurotransmitter-inhibiting peptide that decreases neuronal activity and catecholamine release, giving it Botox-like effects in reducing fine lines and wrinkles, and improving skin firmness [371] safe for cosmetic use [372] Dipeptide Diaminobutyroyl Benzylamide Diacetate a small tripetide with anti-ageing and mattifying effect, stimulates PLOD 3 (procollagen-lysine, oxoglutarate 5-dioxygenase 3), enzyme which is known to be of importance for the intermolecular collagen crosslink stability, increasing the stability of collagen, especially in mature skin [373] * N Palmitoyl Tripeptide improvement of facial wrinkles, elasticity, dermal density and skin tone [374] safe in cosmetic products [375] Vitamins useful role in the treatment of skin ageing and protection of human skin against UV induced ageing [376] Ascorbyl Tetraisopalmitate antioxidant and anti-inflammatory properties, increases skin hydration and smoothness [377] contact dermatitis [378,379] Niacinamide antipruritic, antimicrobial, vasoactive, photoprotective, sebostatic capacity, lightening effect depending on its concentration [380] safe for cosmetic use [381] Panthenol hydrating and softening potential, significantly accelerating epidermal regeneration [382] allergic contact dermatitis [383,384] ...
Article
Full-text available
This study proposes a review on hyaluronic acid (HA) known as hyaluronan or hyaluronate and its derivates and their application in cosmetic formulations. HA is a glycosaminoglycan constituted from two disaccharides (N-acetylglucosamine and D-glucuronic acid), isolated initially from the vitreous humour of the eye, and subsequently discovered in different tissues or fluids (especially in the articular cartilage and the synovial fluid). It is ubiquitous in vertebrates, including humans, and it is involved in diverse biological processes, such as cell differentiation, embryological development, inflammation, wound healing, etc. HA has many qualities that recommend it over other substances used in skin regeneration, with moisturizing and anti-ageing effects. HA molecular weight influences its penetration into the skin and its biological activity. Considering that, nowadays, hyaluronic acid has a wide use and a multitude of applications (in ophthalmology, arthrology, pneumology, rhinology, aesthetic medicine, oncology, nutrition, and cosmetics), the present study describes the main aspects related to its use in cosmetology. The biological effect of HA on the skin level and its potential adverse effects are discussed. Some available cosmetic products containing HA have been identified from the brand portfolio of most known manufacturers and their composition was evaluated. Further, additional biological effects due to the other active ingredients (plant extracts, vitamins, amino acids, peptides, proteins, saccharides, probiotics, etc.) are presented, as well as a description of their possible toxic effects.
... It is also useful in management of post inflammatory hyperpigmentation since it inhibits melanosome transfer. 40 ...
Article
Full-text available
Despite the increasing incidence of adult acne in recent times practical guidelines for management of these patients are lacking in India setup. Thus, to develop practical consensus-based recommendations on diagnosis and management of acne in adult patients an expert panel was finalized. The consensus was developed using Delphi method. Panel members were asked to complete two Delphi surveys one for diagnosis and another for management. Experts reached consensus on practical approach of diagnosis and management of patients with adult acne based on available evidence and their personal experience. Experts recommended that a holistic treatment approach consisting of standard therapy, adjuvant therapy and cosmetic use should be first choice treatment strategy in adult acne patients. Experts also commented that treatment choices should be individualized based on the specific characteristics of each patient and be tailored to suit this particular population.
... The compositions of Emollients 1-3 comply with those of an ideal emollient [1]. Glycerin acts as humectant [6], niacinamide (nicotinamide) as an antipruritic/soothing agent [7,8], and dexpanthenol as a multifunctional ingredient-its functions include the enhancement of epidermal differentiation [1,9]. In addition, Emollients 1-3 contain nonphysiological lipids (argan oil, shea butter, squalane) and physiological lipids (isopropyl isostearate) which act as substitutes for lost natural skin lipids in the outer layers of the SC and contribute to normalization of the altered lipid organization/composition in the SC, respectively [1,[10][11][12]. ...
Article
Full-text available
Three studies were conducted with three new dexpanthenol-containing emollients containing increasing lipid contents (Emollients 1–3) to assess their performances in healthy adults with dry skin. All three studies (N = 42 each) followed virtually the same design. A single skin application of the study product was performed followed by once-daily usage. Skin hydration, transepidermal water loss (TEWL), skin biomechanical properties, and lipid content of the stratum corneum (SC) were regularly assessed over the 28-day study period; a subset (N = 22) underwent a sodium lauryl sulfate (SLS) challenge prior to product application. All three emollients were well tolerated and showed good performances with only minor differences in instrumental measurements. After single and prolonged once-daily applications of Emollients 1–3 to dry skin and dry SLS-damaged skin, skin hydration significantly increased from baseline (BL) (by 38.1–72.4% in unchallenged skin, p < 0.001 for all three). This was paralleled by significant increases in skin elasticity parameters. Usage of Emollients 1 and 3 caused increases from BL in SC cholesterol (by 9.8–12.5%, p < 0.05 for both) and SC free fatty acid levels (by 3.7–26.3%, p < 0.05 for both) at the end of the study. No sustained effects on TEWL were recorded. Our findings support the once-daily use of all three emollients in adults with dry skin.
... Pellagra symptoms include skin dermatitis, dementia, and diarrhea, all of which can be reversed with Nam supplementation. Over the past few decades, Nam has become an important molecule for usage in cosmetic and pharmaceutical products for the treatment of acne, skin photoaging attributes, and skin barrier integrity improvement (Matts et al., 2002;Wohlrab & Kreft, 2014). It has been reported that Nam can protect cells from inflammation, oxidative stress, and metabolic disruption (Sivapirabu et al., 2009;Zhang et al., 2012) and has been found to mitigate some of the acute and chronic damaging effects of UV exposure on skin (Snaidr et al., 2019). ...
Article
Full-text available
Alterations in metabolism in skin are accelerated by environmental stressors such as solar radiation, leading to premature aging. The impact of aging on mitochondria is of interest given their critical role for metabolic output and the finding that environmental stressors cause lowered energy output, particularly in fibroblasts where damage accumulates. To better understand these metabolic changes with aging, we performed an in-depth profiling of the expression patterns of dermal genes in face, forearm, and buttock biopsies from females of 20-70 years of age that encode for all subunits comprising complexes I-V of the mitochondrial electron transport chain. This complements previous preliminary analyses of these changes. "Oxidative phosphorylation" was the top canonical pathway associated with aging in the face, and genes encoding for numerous subunits had decreased expression patterns with age. Investigations on fibroblasts from older aged donors also showed decreased gene expression of numerous subunits from complexes I-V, oxidative phosphorylation rates, spare respiratory capacity, and mitochondrial number and membrane potential compared to younger cells. Treatment of older fibroblasts with nicotinamide (Nam) restored these measures to younger cell levels. Nam increased complexes I, IV, and V activity and gene expression of representative subunits. Elevated mt-Keima staining suggests a possible mechanism of action for these restorative effects via mitophagy. Nam also improved mitochondrial number and membrane potential in younger fibroblasts. These findings show there are significant changes in mitochondrial functionality with aging and that Nam treatment can restore bioenergetic efficiency and capacity in older fibroblasts with an amplifying effect in younger cells.
... The nicotinamide chitosan nanoparticles were more powerful on inflammatory lesions than on comedones, as evident from the significant higher percentage reduction for the former compared to the latter (P b 0.05), which might be attributed to the particular anti-inflammatory nature of nicotinamide [38,39], as well as the expected anti-inflammatory properties of chitosan [40]. In addition to its anti-inflammatory properties, nicotinamide was reported to be a promising anti-acne agent since it decreases sebum production and its inhibitory effect on Propionibacterium acnes [41][42][43][44]. Interestingly, chitosan polymer itself has an adjunctive anti-acne activity by virtue of its antibacterial action against two causative bacteria; Propionibacterium acnes and Staphylococcus aureus [45]. ...
Article
Despite the popularity of chitosan as a biodegradable polymer used in a variety of applications, clinical trials involving chitosan or its nanoparticles are still scarce. Moreover, the use of nutraceuticals as a replacement to conventional chemical treatments has become currently popular, and if combined with nanotechnology, nutraceuticals can achieve a comparable or even better therapeutic outcome. In the current work, chitosan nanoparticles loading the nutraceutical nicotinamide were optimized, characterized, and clinically tested on patients suffering from acne vulgaris. The topical merits of chitosan nanoparticles were proven, in which they exhibited strong skin adhesion ex vivo and high nicotinamide deposition in the different skin layers (stratum corneum, epidermis and dermis) amounting to a total of 68%. When clinically tested on patients, nicotinamide nanoparticles displayed 73% reduction in the inflammatory acne lesions compared to untreated areas, hence proving that chitosan nanoparticles can be a clinically sounding option for treatment of skin diseases.
... Nicotinamide (Nam; aka niacinamide, vitamin B3) has been used for decades in cosmetic and pharmaceutical products for the treatment of acne, skin photoaging attributes, and barrier integrity improvement [12][13][14]. It has been reported that Nam can protect cells from oxidative stress, UVinduced immunosuppression, and metabolic disruption [15][16][17]. ...
Preprint
Daily exposure of skin to environmental stressors leads to molecular and morphological changes ascribed as premature aging. These stressors include solar radiation, industrial pollution, fossil fuel and carbon emissions, which cause cellular damage that induces an inflammatory response in skin. Several inflammatory components are known to be involved in triggering the senescence-associated secretory phenotype (SASP) which is known to accelerate aging. It is hypothesized that preventing induction of inflammation by environmental stressors can prevent premature aging. Since it is known that nicotinamide (Nam) has anti-inflammatory properties, we tested whether Nam can inhibit environmental stressor-induced inflammation. Exposure of keratinocytes to UVB, urban dust, diesel exhaust, and cigarette smoke extract stimulated production of the inflammatory mediators PGE2, IL-6, and IL-8 and induced gene expression patterns associated with apoptosis, DNA repair, and cell cycle control. In all cases, Nam treatment significantly inhibited these stress-induced responses. Nam also reduced IL-8 levels stimulated by the combination of topically applied particulate matter (PM2.5) and UV exposure in 3D skin equivalents. Under 5% 02 conditions that more closely mimic physiological 02 levels, Nam had a heightened inhibitory effect on UVB-induced PGE2 levels in keratinocytes. In a UV-challenge study, treatment with Nam reduced skin surface IL-1RA/IL-1 inflammatory biomarkers and erythema that were induced by solar simulated radiation. These findings provide a body of evidence that Nam can mitigate in part the skin’s inflammatory response elicited by exposure to environmental stressors. This supports the potential that Nam can inhibit premature aging and help maintain skin’s functionality and appearance.
... The authors were specific to call out that Nam is not considered to be a hair growth promoter. Although the authors reported data that 0.1% Nam treatment had a statistically significant increase in hair thickness and density when compared to baseline, it is difficult to conclude that 0.1% Nam actually had a relevant effect on hair biology properties for the following reasons: (1) the lack of a placebo control renders the conclusions non-relevant that Nam can stimulate hair growth because it is well known that a placebo treatment can have a directionally positive effect on hair growth [3]; (2) 0.1% Nam is an order of magnitude lower in concentration than what is typically tested in dermatology-related studies [4,5]. Minoxidil, one of the only two FDA-approved hair growth molecules, needs to be applied at 2-5% to attain efficacy. ...
Article
Full-text available
This letter is intended to clarify misconceptions in the consumer world on the alleged side effects of niacinamide (Nam) on hair growth properties. It is important that the overall body of evidence related to Nam and hair biology be reviewed so as not to confuse consumers and patients on Nam impact on facial and body hair. We have reviewed the published literature and provide new data to demonstrate that Nam has a neutral, if any, impact on hair growth properties.
... Niacinamide (NIA) is the water-soluble form of vitamin B3 (Figure 1). Since its discovery as a "pellagra-preventing" agent, this molecule has been widely used in personal care and cosmetic products [1,2]. NIA has been demonstrated to have a number of anti-inflammatory and photo-protective effects following topical application. ...
Article
Full-text available
Niacinamide (NIA) is the amide form of vitamin B3 and has been widely used in pharmaceutical and personal care formulations. Previously, we reported a comparative study of NIA permeation from neat solvents using the Skin Parallel Artificial Membrane Permeability Assay (PAMPA) and mammalian skin. A good correlation between NIA permeation in the different models was found. In the present work, ten binary and ternary systems were evaluated for their ability to promote NIA delivery in the Skin PAMPA model, porcine skin and human epidermis. Penetration enhancement was evident for binary systems composed of propylene glycol and fatty acids in human skin studies. However, propylene glycol and oleic acid did not promote enhancement of NIA compared with other systems in the Skin PAMPA model. A good correlation was obtained for permeation data from Skin PAMPA and porcine skin. However, data from the Skin PAMPA model and from human skin could only be correlated when the PG-fatty acid systems were excluded. These findings add to our knowledge of the potential applications of Skin PAMPA for screening dermal/transdermal preparations.
... Similar mechanisms are also suspected in BP [32]. Both niacinamide and tetracycline inhibit the activity of proteases and have a wide range of anti-inflammatory properties such as inhibiting the chemotaxis of leukocytes and secretion of proinflammatory cytokines [9][30] [34]. This drug combination was originally reported in humans for the treatment of cutaneous lupus and has been used to treat DLE in dogs for the past 2 decades [18]. ...
Article
Mucous membrane pemphigoid was diagnosed in a 2.5-year-old male intact foxhound-beagle cross which was presented with an acute onset of non-pruritic, multifocal, slowly progressive erosive-ulcerative dermatitis predominantly affecting the nasal planum, eyelids and muzzle with multiple vesicles on the inner pinnae, oral mucosa and tongue. The diagnosis was based on clinical signs and histological examination of skin biopsies. The patient did not respond to immunosuppressive prednisolone therapy, but went into complete remission with oral doxycycline and niacinamide and stayed in remission on long-term exclusive niacinamide treatment. © Georg Thieme Verlag KG Stuttgart · New York.
... Up to 4% (Damian, 2010) Anti-inflammatory, antipruritic, lightening, antimicrobial, photoprotective (Wohlrab & Kreft, 2014). vitamin E 0.5 to 1% (Keen & Hassan, 2016) Antioxidant, skin aging, treatment of granuloma annulare, reducing dark under-eye circles (Keen & Hassan, 2016). ...
Article
Full-text available
Ultraviolet (UV) filters such as octocrylene and oxybenzone in topical photoprotection products work effectively in absorbing UV radiation, thus minimizing sun damage to the skin. Antioxidants are incorporated into sunscreen products to enhance the photoprotection ability of the products. However, the effectiveness of the antioxidants on the sun protection factor (SPF) of UV filters is not well established. Hence in this study, the effect of caffeine, nicotinamide, β-carotene, α-tocopherol, and cactus extract on the SPF of octocrylene and oxybenzone were investigated. The UV absorbance of octocrylene (5 µg/mL) and oxybenzone (20 µg/mL) in 95% ethanol, with different concentrations of the antioxidants (0.1-100 µg/mL) and cactus extract were measured from 290-320nm. The UV absorbance values were converted to SPF values by the Mansur equation. Statistical analysis was performed by ANOVA test and Post Hoc test (Dundett T3 test) with a significance level of p<0.05 using SPSS software. The antioxidants and cactus extract were found to significantly increase the SPF of octocrylene and oxybenzone solutions in a concentration-dependent manner. Out of the antioxidants tested, β-carotene and α-tocopherol were the most effective antioxidants to increase the SPF of octocrylene solution and oxybenzone solutions, respectively. The results supported that it is beneficial to incorporate antioxidants and cactus extract into the formulation of topical photoprotection products.
... 13 Niacinamide is characterized by its lightening e ect due to its ability to block, in a reversible manner, the transfer of melanosomes from melanocytes into keratinocytes. 14 The antiaging treatment regimen used in this study comprises two formulations that utilize the RST and EDAT technologies: one formulation contains a high concentration of retinoids (high-concentration formulation) and is designed to treat photoaging, while the other formulation contains a high concentration of moisturizing and soothing ingredients (transition cream) and is designed to help the skin gradually adapt to the high-concentration formula. These two products were developed as anhydrous, semiocclusive formulations to increase the degree of emolientia and hydration and facilitate the di usion of the active ingredients in the stratum corneum. ...
Article
Background. Effects of environmental contaminents, such as air pollution and cigarette smoking on skin include increased oxidation, subclinical inflammation, and degradation of the dermal matrix, which can accelerate the skin aging process. Objective. An open-label, prospective study was conducted to assess the efficacy and tolerability of a topical anti-aging regimen comprising high-concentration retinoids, Deschampsia antarctica extract, and niacinamide in participants living in a heavily polluted (Level III, World Health Organization) city. Methods. Twenty-two female Caucasian volunteers with Fitzpatrick Skin Types III and IV were treated for 90 days with the topical anti-aging regimen. Subjective clinical assessments using the Rao-Goldman Scoring for Facial Aging, Patient's Global Assessment (PGA), and Investigator's Global Assessment (IGA). Additionally, objective instrumental assessments for wrinkles using Visia® (Canfield Scientific, Parsippany, New Jersey) and Visioline® (Courage+Khazaka Electronic GmbH, Cologne, Germany) and viscoelasticity and firmness using Cutometer® (Courage+Khazaka Electronic GmbH ) were completed at baseline, Day 30, and Day 90. Results. At Day 30, wrinkles in the periocular area significantly improved by 35.7 percent (p=0.003) compared to baseline. At the end of the study (Day 90), a significant improvement in firmness (41.7%) and viscoelasticity (12.8%) were observed. Tolerance for treatment was assessed as "good" or "very good" in 86.5 percent of the volunteers. Conclusion. This novel antiaging treatment regimen could potentially serve as an effective and long-term topical treatment option for improving signs of facial aging and protecting the skin from external factors associated with acceleration of the skin aging process, such exposure to UV radiation, air pollution, and cigarette smoke. Larger and longer-term, randomized, controlled clinical trials in more diverse population samples are needed to confirm our results.
... Nicotinamide, an endogenous inhibitor of PARP-1, has been reported that it plays significant roles in cellular protection and in determining cellular fate in response to genotoxic DNA damage (Surjana et al. 2010). Recently, niacinamide as an amide of niacin therefore reduces the levels of oxidative stress, apoptosis, and PARP-1 activity in Aβ 1 -42 -induced rat model of Alzheimer's disease (Wohlrab and Kreft 2014). Hence, the relationship between PARP-1 inhibition and N2L related to cell apoptosis deserves to be investigated in future research. ...
Article
Full-text available
β-amyloid protein (Aβ) is thought to be the primary cause of the pathogenesis of Alzheimer’s disease (AD). Niacin has been reported to have beneficial effects on AD. Previously, we synthesized a novel compound lipoicacid–niacin dimer (N2L) and revealed that it had potent blood-lipid regulation and antioxidative properties without aflushing effect. Given that lipid metabolism is also associated with AD, the present study aimed to investigate the neuroprotective effects of N2L on Aβ1–42-induced cytotoxicity in HT22 cells. We found that N2L significantly attenuated cell apoptosis, MDA level, ROS content, and the mitochondrial membrane potential corruption induced by Aβ1–42 in HT22 cells. In addition, the activities of SOD, GSH-px and CAT that were decreased by Aβ1–42 were also restored by N2L. Furthermore, N2L reduced proapoptotic signaling by increasing the expression of anti-apoptotic Bcl-2 and decreasing the protein expression of both pro-apoptotic Bax and cleaved Caspase-3. Together, these findings indicate that N2L holds great potential for neuroprotection against Aβ1–42-induced cytotoxicity via inhibition of oxidative stress and cell apoptosis, suggesting that N2L may be a promising agent for AD therapy.
... Pre-clinical published studies have shown that niacinamide has the potential for topical application in cosmetic preparations [6], where it can increase the levels of ceramides, free fatty acids and cholesterol in the SC [7], and decrease sebum production [8]. In clinical studies, topical preparations with niacinamide were shown to reduce sebum production [9], to be effective in subjects with oily skin [10], and to return the altered skin barrier to normal levels in subjects with acne [11]. ...
Article
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.
... 38,39 In vivo experiments, DOX in combination with NAM inhibited the growth of K562R xenografts more efficiently than either NAM or DOX alone, and NAM enhanced DOX mediated activation of caspase-3 and PARP. There was no significant difference observed in the body weight of mice in each group, at the same time, combined with other reports [40][41][42] suggesting low toxicity and safety of NAM in mice, implicated the NAM potential value as clinically useful drugs in CML patients with drug resistance. A well-known side effect of DOX is cardiotoxicity 43 and research shows that NAM can relieve the related cardiac toxicity to some extent. ...
Article
Full-text available
The NAD‐dependent deacetylase Sirtuin 1 (SIRT1) plays a vital role in leukemogenesis. Nicotinamide (NAM) is the principal NAD+ precursor and a noncompetitive inhibitor of SIRT1. In our study, we showed that NAM enhanced the sensitivity of chronic myeloid leukemia (CML) to doxorubicin (DOX) via SIRT1. We found that SIRT1 high expression in CML patients was associated with disease progression and drug resistance. Exogenous NAM efficiently repressed the deacetylation activity of SIRT1 and induced the apoptosis of DOX‐resistant K562 cells (K562R) in a dose‐dependent manner. Notably, the combination of NAM and DOX significantly inhibited tumor cell proliferation and induced cell apoptosis. The knockdown of SIRT1 in K562R cells enhanced NAM+DOX‐induced apoptosis. SIRT1 rescue in K562R reduced the NAM+DOX‐induced apoptosis. Mechanistically, the combinatory treatment significantly increased the cleavage of caspase‐3 and PARP in K562R in vitro and in vivo. These results suggest the potential role of NAM in increasing the sensitivity of CML to DOX via the inhibition of SIRT1. In summary, NAM sensitized K562 and K562R cells to DOX, which by facilitating the activation of caspase‐3/PARP and SIRT1 inhibition might pave the way for the development of a potential adjunct in the treatment of blast crisis CML patients.
Article
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.
Article
The microneedling technique was initially introduced for skin rejuvenation in cosmetology. The technique is minimally invasive and therefore explored for the treatment of multiple dermatological conditions. High effectiveness, very less side effects and quick recovery time are the benefits of skin microneedling as a cosmetic, and medical treatment. Over the last two decades, the applications of microneedling in skin science have grown drastically. The technique is effective in the treatment of acne scar, vitiligo, alopecia, melasma, and skin cancer. The current review focuses on the cosmetic as well as therapeutic applications of microneedling for the treatment of various skin problems.
Article
Background: Individual B vitamins have many favourable effects on the skin and are common cosmetic ingredients. However, their formulation is demanding due to stability issues, which consequently affect the products´ quality. Aims: We aimed to determine the quality (labelling accuracy, content determination, and content-related quality control) and stability under long-term and accelerated storage conditions of a representative sample of commercial cosmetics containing the most common B vitamins - nicotinamide, dexpanthenol, pyridoxine, and cyanocobalamin. Methods: Cyanocobalamin was determined by a previously published stability-indicating HPLC-DAD method for the simultaneous determination of all hydrophilic vitamins. This method was additionally simplified and adjusted for the time-effective analysis of nicotinamide, dexpanthenol, and pyridoxine. Both methods were properly validated. Results: All labelled B vitamins were present in the 36 tested products, mostly in contents, reported effective on the skin. Thus, a straightforward correlation between vitamin contents and product prices was not observed. The content-related quality control of eight products, which quantitively specify their content, revealed significantly lower nicotinamide contents (47% and 57%) in two products and appropriate or higher nicotinamide (102-112%) and dexpanthenol (100-104%) contents than declared in the remaining products. The 6-month long-term and accelerated stability studies demonstrated the products' physical stability, but also revealed dexpanthenol, pyridoxine, and cyanocobalamin degradation, while nicotinamide was mostly stable in the tested products. Conclusions: The obtained results provide an inside into the quality of commercial vitamin B cosmetics and highlight the importance of stability testing in the formulation of quality, efficient and safe cosmetics.
Article
Full-text available
Introduction: Melasma is a very common and difficult to treat hypermelanosis because it usually responds poorly to therapies, negatively affecting the quality of life of patients. Objective: to know and analyze the scientific evidence related to the treatment of patients with facial melasma treated with niacinamide. Method: a literature review was performed based on a data search in BIREME, PubMed, SciELO and ScienceDirect. Articles indexed in these electronic journals were included in the time frame from 2011 to 2019. Results: Evidence analyzes revealed a major impact on the appearance of facial melasma after niacinamide treatment. Well, the studies (100%) concluded improvement of the spots with the treatment time, improving the appearance of the skin. Conclusion: Evidence shows that niacinamide has a lightening property in adult women with improvement of melanic hyperpigmentation caused by melasma. However, there is very little evidence published in the last decade using pure niacinamide for increased pigmentation in melasma.
Article
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.
Article
Full-text available
Article
Full-text available
Chitin nanofibrils (CN) and nanolignin (NL) were used to embed active molecules, such as vitamin E, sodium ascorbyl phosphate, lutein, nicotinamide and glycyrrhetinic acid (derived from licorice), in the design of antimicrobial, anti-inflammatory and antioxidant nanostructured chitin nanofibrils–nanolignin (CN-NL) complexes for skin contact products, thus forming CN-NL/M complexes, where M indicates the embedded functional molecule. Nano-silver was also embedded in CN-NL complexes or on chitin nanofibrils to exploit its well-known antimicrobial activity. A powdery product suitable for application was finally obtained by spray-drying the complexes co-formulated with poly(ethylene glycol). The structure and morphology of the complexes was studied using infrared spectroscopy and field emission scanning electron microscopy, while their thermal stability was investigated via thermo-gravimetry. The latter provided criteria for evaluating the suitability of the obtained complexes for subsequent demanding industrial processing, such as, for instance, incorporation into bio-based thermoplastic polymers through conventional melt extrusion. In vitro tests were carried out at different concentrations to assess skin compatibility. The obtained results provided a physical–chemical, morphological and cytocompatibility knowledge platform for the correct selection and further development of such nanomaterials, allowing them to be applied in different products. In particular, chitin nanofibrils and the CN-NL complex containing glycyrrhetinic acid can combine excellent thermal stability and skin compatibility to provide a nanostructured system potentially suitable for industrial applications.
Article
The exposome has an impact on skin from life-long exposure. Acute short-term exposure to exposome stressors can also alter skin functions such as skin physical barrier and immune defenses, leading to skin dryness, sensitivity, flares of inflammatory skin conditions, or viral reactivations. Probiotics are defined as live microorganisms, which, when administered in adequate amounts, confer a health benefit on the host. An extract produced by lysing Vitreoscilla filiformis (VfeV) cultured in Vichy volcanic mineralizing water (VVMW) has properties of probiotic fractions. In this review, we present in vivo and ex vivo studies with a dermocosmetic formulation containing 80% VVMW, 5% VfeV, 4% niacinamide (vitamin B3), 0.4% hyaluronic acid, and 0.2% vitamin E (M89PF) to evaluate the clinical efficacy in preventing and repairing stressed skin. Skin barrier benefits of M89PF were shown in studies after the skin was exposed to sudden thermal changes, after skin irritation by tape stripping, and in sleep-deprived women. M89PF significantly accelerated skin renewal compared to untreated skin. Skin antioxidant defense activity of M89PF was shown after exposure to stress from UVA plus cigarette smoke aggression. Skin microbiome recovery after acute stress from a harsh cleanser was significantly better in M89PF-treated skin compared to bare skin. Clinical benefits of M89PF on correcting clinical signs of stressed skin were shown in both Caucasian and Asian women exposed to a stressful lifestyle and various external (pollution, tobacco smoking, solar radiation) and internal (poor sleep, stressful work, unbalanced diet, and alcohol consumption) exposome factors. M89PF also showed depigmenting properties on dark spots in Asian women. Further clinical studies are now warranted to evaluate the efficacy of M89PF as adjuvant care to prevent and repair skin barrier disruption and reinforce skin defenses in skin exposed to acute stresses.
Article
Background The prevalence and scope of dermatological illness differ from region to region. Based upon type and severity, the conditions may vary from superficial to deep systemic skin infections. Niacinamide, an amide analog of vitamin B3 which was conventionally utilized as a food supplement, is now explored for the management of skin disorders. Being a powerhouse on its own, it is not stored inside the body naturally and has to be acquired from external sources. Areas covered This review is an attempt to disclose the physiology, pharmacology, and highlight the dermatological potentials of niacinamide, discussing its pharmacological mechanisms, varied commercially available treatments, and novel approaches, i.e., in research and patented formulations. Results Niacinamide has been verified in treating almost every skin disorder, viz. aging, hyperpigmentation, acne, psoriasis, pruritus, dermatitis, fungal infections, epidermal melasma, non-melanoma skin cancer, etc. It has been reported to possess numerous properties, for instance, anti-inflammatory, antimicrobial, antioxidant, antipruritic, and anticancer, which makes it an ideal ingredient for varied dermal therapies. Long term use of niacinamide, regardless of the skin type, paves the way for new skin cells, makingskin healthier, brighter, and hydrated. Conclusion Niacinamide possesses a variety of positive characteristics in the field of dermatology. Novel approaches are warranted over current treatments which could bypass the above shortcomings and form an effective and stable system. Hence, niacinamide has the potential to become an individual and a productive component with wide future scope.
Article
Although relatively uncommon, autoimmune bullous diseases carry the risk of increased mortality and can significantly impact quality of life. This group of diseases is broad and encompasses subepidermal conditions like bullous pemphigoid, cicatricial pemphigoid, epidermolysis bullosa acquisita, dermatitis herpetiformis, and linear IgA bullous dermatosis, as well as intraepidermal conditions like pemphigus and its variants. The pathophysiology of each condition is incompletely understood but broadly involves the formation of autoantibodies targeting skin adhesion proteins, a process which relies on a complex interplay between a dysregulated immune system, genetic predisposition, and environmental factors. We review the impact of nutrition on pathogenesis, clinical course, and treatment of various autoimmune bullous diseases.
Article
Full-text available
Vitamins are micronutrients which form an essential part of our diet. They are needed for healthy functioning of metabolic activities, some forms of vitamin form basis for our immunity and bone building. Usually essential nutrients cannot be synthesised in our bodies, hence we need to obtain them from our diet. Many Vitamin groups have been studied extensively for the pharmacological effects. Many studies have proved the effectiveness of combination therapies of vitamins with other medication for treatment of various diseases. This review presents all the studies conducted to prove the therapeutic effects of vitamins. Keywords: Multivitamins, Vitamin A, Vitamin B, Vitamin C, Vitamin D, Ginseng, Niacinamide, Antibiotics, Cefuroxime, DAV Therapy.
Article
Particulate matter (PM) is a common indirect indicator of air pollution and threatens public health upon prolonged exposure, leading to oxidative stress, increasing the risk of develop respiratory and cardiovascular, as well as several autoimmune diseases and cancer. Nowadays, as a first line defense against PM, skin health attracted much attention. Our review summarized the skin damage mechanism induced by PM, including damage skin barrier directly, reactive oxygen species (ROS) accumulation, autophagy, and two canonical signaling pathways. Furthermore, ROS and oxidative stress have been considered pathogenesis centers, with essential skin damage roles. Extracts from plants and natural compounds which present high antioxidant capacity could be used to treat or protect against air pollution-related skin damage. We conclude the extracts reported in recent studies with protective effects on PM-mediated skin damage. Besides, the mechanism of extracts' positive effects has been revealed partially.
Chapter
The complicated and multifactorial nature of acne pathophysiology provides a multitude of opportunities for vitamins and minerals to disrupt the inflammatory cascade. In their traditional roles as dietary necessities, vitamins and minerals participate in keratinocyte proliferation and maturation, modulation of lipid production in human sebocytes, and inhibition of pro-inflammatory cytokines, matrix metalloproteinases, and antimicrobial peptides, as well as act as antioxidants. Not surprisingly, then, there is considerable in vitro and preclinical data predicting their efficacy in acne. Although conclusive clinical evidence is currently lacking for many of them, more vigorous trials are being conducted with increasingly convincing in vivo data. At this time, data for vitamin A analogs, zinc, and niacinamide is most compelling. It may well be that combination therapy will be more efficacious than monotherapy. Fortunately, due to their large safety margin, we can afford to be generous with our recommendations while awaiting more definitive results.
Article
Full-text available
Acne is a kind of chronic inflammatory skin disease, which is common in the hair follicle and sebaceous gland of teenagers. It often recurs and affects the quality of life of patients. Acne itself can cause the damage of skin barrier function. On the other hand, common acne treatment methods, such as external drugs, systemic drugs, physical and chemical treatment, can also lead to the damage of skin barrier function and affect the treatment effect. The application of skin care in the adjuvant treatment of acne has been widely concerned. Due to their high safety, good tolerance and the effect of improve the damaged skin barrier, medical skin care products are a hot spot in the treatment of cosmetic skin diseases in recent years. It can not only increase the curative effect, reduce the side effectsbut alsoincrease the compliance of patients when combined with conventional acne treatment. In this paper, skin care products and their application in acne treatment were reviewed. This article is protected by copyright. All rights reserved.
Article
Objective To evaluate whether niacinamide (Nam) can mitigate production of inflammatory and senescence‐related biomarkers induced by environmental stressors. Methods Human epidermal keratinocytes were exposed to UVB, urban dust, diesel exhaust, and cigarette smoke extract and treated with Nam or vehicle control. Full thickness 3‐D skin organotypic models were exposed to a combination of UVB and PM2.5 and treated with Nam or vehicle control. Quantitation of the SASP‐related inflammatory mediators PGE2, IL‐6, and IL‐8 was performed on cultured media. UVB‐exposed keratinocytes treated with and without Nam were immunostained for the senescence biomarker Lamin B1 (LmnB1). Transcriptomics profiling of cigarette smoke extract effects on keratinocytes was performed. A placebo controlled double blinded clinical was conducted on 40 female panelists that were pretreated on back sites for two weeks with 5% Nam or vehicle and then exposed to 1.5 minimal erythemal dose (MED) solar simulated radiation (SSR). Treated sites were compared to non‐treated exposed sites for erythema and the skin surface IL‐1αRA/IL‐1α inflammatory biomarkers. Results UVB induced synthesis of PGE2, IL‐8 and IL‐6 and reduced LmnB1 levels in keratinocytes. Urban dust and diesel exhaust only stimulated synthesis of IL‐8 whereas cigarette smoke extract only stimulated levels of PGE2. In all exposures, treatment with Nam significantly mitigated synthesis of the inflammatory mediators and restored levels of UVB‐reduced LmnB1. In the 3D skin equivalent model, Nam reduced IL‐8 levels stimulated by a combination of topical PM2.5 and UV exposure. In a UV‐challenge clinical, pretreatment with 5% Nam reduced erythema and skin surface IL‐1αRA/IL‐1α inflammatory biomarkers that were induced by SSR. Conclusion Since it is known that Nam has anti‐inflammatory properties, we tested whether Nam can inhibit environmental stress induced inflammation and senescence‐associated secretory phenotype (SASP) biomarkers. We show Nam can reduce PGE2, IL‐6, and IL‐8 levels induced by environmental stressors. Additionally, in vivo pretreatment with Nam can reduce UV‐induced erythema and skin surface inflammatory biomarkers. These findings add to the body of evidence that Nam can mitigate the skin’s inflammatory response elicited by environmental stressors. This supports Nam can potentially inhibit senescence and premature aging and thereby maintain skin’s functionality and appearance.
Article
Metabolic disorders, such as diabetes mellitus (DM), are increasingly becoming significant risk factors for the health of the global population and consume substantial portions of the gross domestic product of all nations. Although conventional therapies that include early diagnosis, nutritional modification of diet, and pharmacological treatments may limit disease progression, tight serum glucose control cannot prevent the onset of future disease complications. With these concerns, novel strategies for the treatment of metabolic disorders that involve the vitamin nicotinamide, the mechanistic target of rapamycin (mTOR), mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), AMP activated protein kinase (AMPK), and the cellular pathways of autophagy and apoptosis offer exceptional promise to provide new avenues of treatment. Oversight of these pathways can promote cellular energy homeostasis, maintain mitochondrial function, improve glucose utilization, and preserve pancreatic beta-cell function. Yet, the interplay among mTOR, AMPK, and autophagy pathways can be complex and affect desired clinical outcomes, necessitating further investigations to provide efficacious treatment strategies for metabolic dysfunction and DM.
Article
Sensitive skin has traditionally been viewed as a cosmetic problem or as a purely psychosomatic alteration with a major subjective component. Different studies of its pathophysiologic etiology, however, have shown it to be a complex entity that several authors now consider to be a neurodermatological syndrome. Because of this complexity, skin sensitivity can be difficult to diagnose and treat, particularly considering that it may present with another disease. Simple tools applicable to clinical practice are thus necessary to identify and manage this disease as an independent entity. In this study, we perform a practical review of the most recent scientific advances in the area of sensitive skin that justify it being considered an individual entity, and provide tools for its identification and treatment. We propose diagnostic and treatment algorithms based on evidence from the literature and our experience and expertise.
Article
Full-text available
Niacinamide (NIA) is a water-soluble vitamin that is widely used in the treatment of skin diseases. Moreover, NIA displays antioxidant effects and helps repair damaged DNA. Recent studies showed that particulate matter 2.5 (PM2.5) induced reactive oxygen species (ROS), causing disruption of DNA, lipids, and proteins; mitochondrial depolarization, and apoptosis of skin keratinocytes. Here, we investigated the protective effects of NIA on PM2.5-induced oxidative stress in human HaCaT keratinocytes. We found that NIA could inhibit the ROS generation induced by PM2.5, as well blocked the PM2.5-induced oxidation of molecules, such as lipids, proteins, and DNA. Furthermore, NIA alleviated PM2.5-induced accumulation of cellular Ca2+, which caused cell membrane depolarization and apoptosis, and reduced the number of apoptotic cells. Collectively, the findings show that NIA can protect keratinocytes from PM2.5-induced oxidative stress and cell damage.
Article
Resumen Tradicionalmente, la piel sensible se ha considerado como un problema cosmético o como una alteración puramente psicosomática con un fuerte componente subjetivo. Sin embargo, diversos estudios científicos sobre sus procesos fisiopatológicos y su etiopatogenia han demostrado que se trata de una entidad compleja que ya diversos autores consideran un síndrome neurodermatológico. Sus características hacen que su diagnóstico y tratamiento puedan resultar complicados en la práctica clínica habitual, siendo necesarias herramientas sencillas que se puedan usar de rutina, tanto para identificar esta entidad, que puede presentarse acompañada de otra patología, como para su manejo independiente. En este trabajo realizamos una revisión práctica de los avances científicos más recientes el campo de la piel sensible que justifican su consideración individual y ofrecen herramientas para identificarla y tratarla. Proponemos algoritmos de diagnóstico y de tratamiento basados en las evidencias de la literatura y en la opinión de los expertos que firman este artículo.
Article
Full-text available
Without known mechanisms of action, Crohn's disease is exacerbated, and ulcerative colitis is improved, by the use of tobacco. Mycobacterium avium subspecies paratuberculosis (MAP) may be zoonotic. We hypothesized that tobacco components might alter the growth kinetics of MAP, explaining these divergent clinical observations. The effect of nicotine, nicotinic acid, nicotinamide and α and β nicotinamide adenine dinucleotide (α and β NAD) were studied on eight strains of three mycobacterial species (MAP, M. avium and M. tb. complex). Data are obtained as "cumulative growth index," (cGI) and presented as "percent increase in cumulative GI" (% + ΔcGI). Nicotinic acid enhances the two human MAP isolates (Dominic; 225% + ΔcGI and UCF-4; 92% + ΔcGI) and M. avium (ATCC 25291; 175% + ΔcGI). Nicotinamide (at 6.4 µg/ml) enhances the human MAP isolates (Dominic; 156% + ΔcGI and UCF-4; 79% + ΔcGI) and M. avium (ATCC 25291; 144% + ΔcGI.) Both α and β NAD enhance Dominic; (135 and 150 % + ΔcGI) and UCF-4; (81 and 79% + ΔcGI). At the doses tested, nicotine has no effect on any strain studied. We show enhancement of MAP growth by nicotinic acid, one of ≥4,000 tobacco-related molecules, its amide, nicotinamide and α and β NAD. Pure nicotine has no enhancing effect at the doses studies.
Article
Full-text available
Nicotinamide, the amide form of vitamin B(3) (niacin), is changed to its mononucleotide compound with the enzyme nicotinic acide/nicotinamide adenylyltransferase, and participates in the cellular energy metabolism that directly impacts normal physiology. However, nicotinamide also influences oxidative stress and modulates multiple pathways tied to both cellular survival and death. During disorders that include immune system dysfunction, diabetes, and aging-related diseases, nicotinamide is a robust cytoprotectant that blocks cellular inflammatory cell activation, early apoptotic phosphatidylserine exposure, and late nuclear DNA degradation. Nicotinamide relies upon unique cellular pathways that involve forkhead transcription factors, sirtuins, protein kinase B (Akt), Bad, caspases, and poly (ADP-ribose) polymerase that may offer a fine line with determining cellular longevity, cell survival, and unwanted cancer progression. If one is cognizant of the these considerations, it becomes evident that nicotinamide holds great potential for multiple disease entities, but the development of new therapeutic strategies rests heavily upon the elucidation of the novel cellular pathways that nicotinamide closely governs.
Article
Full-text available
Type 1 diabetes is a chronic disease characterized by the selective destruction of insulin-producing cells in the pancreas. Enterovirus (EV) is the prime candidate to initiate this destruction and several inflammatory chemokines are induced by EV infection. Nicotinamide has been shown to protect isolated human islets, and to modulate chemokine expression. The aim of this study was to evaluate the effect of nicotinamide on EV replication and EV-induced chemokine secretion and cytolysis of human islets. Two EV strains were used to infect human islets in vitro, one lytic (Adrian) isolated from a child at onset of type 1 diabetes, and one non-lytic (VD2921). Secretion of the chemokines IP-10 and MCP-1, viral replication, and virus-induced cytopathic effect (CPE), were measured at different time points post-infection. Addition of nicotinamide to the culture medium reduced viral replication and virus-induced islet destruction/CPE, significantly. Both EV strains increased secretion of IP-10 and MCP-1, when measured days 2-3, and days 5-7 post infection, compared to mock-infected control islets. IP-10 was not produced by uninfected isolated islets, whereas a basal secretion of MCP-1 was detected. Interestingly, addition of nicotinamide blocked completely (Adrian), or reduced significantly (VD2921), the virus-induced secretion of IP-10. Secretion of MCP-1 was also reduced in the presence of nicotinamide, from infected and uninfected islets. The reported antiviral effects of nicotinamide could have implications for the treatment/prevention of virus- and immune-mediated disease. Also, this study highlights a possible mechanism of virus-induced type 1 diabetes through the induction of MCP-1 and IP-10 in pancreatic islets.
Article
Full-text available
Hyperbaric oxygen has been established as an acceptable treatment for the chronic healing wound. Nicotinamide has been shown to be angiogenic and accelerate the physiologic process following wounding. Therefore both nicotinamide and hyperbaric oxygen were evaluated to enhance flap survival in an island pedicle skin flap model. These two treatment modalities were evaluated alone and in combination to assess if there is an addictive effect to enhance flap survival. Forty Sprague-Dawley male rats (weight 300-350 grams) were treated for 14 days preoperatively 1 day post-operatively with either 400 mg of nicotinamide i.p. or saline i.p. On day 14, a 7 X 7 cm island pedicle skin flap was elevated ligating the left inferior epigastric neurovascular pedicle and were sutured in their normal position. Twenty animals then underwent hyperbaric oxygen treatments. Forty-eight hours post-operatively animals were re-anesthetized and were given a single injection of fluorescein (25 mg/kg) via the tail vein. The % survival of the flap and SEM of the groups are as follows: Saline 45.67 +/- 31.14, nicotinamide 85.30 +/- 9.24, saline-hyperbaric oxygen 76.70 +/- 9.42 and nicotinamide-hyperbaric oxygen 90.86 +/- 3.94 with statistical significance of p less than 0.01. Nicotinamide appears to be another acceptable therapeutic modality in the management of the acceleration of wound healing.
Article
Full-text available
Phorbol ester-induced promotion of initiated NMRI mouse skin keratinocytes to papillomas could be largely prevented when nicotinamide-like inhibitors of poly(ADP-ribose)polymerase (nicotinamide, benzamide, 3-aminobenzamide) were applied simultaneously with 12-O-tetradecanoylphorbol-13-acetate (TPA). A similar suppression of tumor promotion by nicotinamide analogues was demonstrated in clone 41 JB6 epidermal cells which are promotable by TPA to anchorage-independent growth. The antipromotion effect of nicotinamide analogues, however, does not appear to come about by an inhibition of poly(ADP-ribose)polymerase. Acid analogues of nicotinamide, such as benzoic acid or 3-aminobenzoic acid which do not inhibit the polymerase, showed antipromotion activity similar to that of their corresponding amides. It could also be ruled out that these antipromoters mediate their effect on keratinocytes by a cytostatic action, by scavenging the promoter TPA in a chemical reaction, or by inhibiting protein kinase C. In initiated mouse skin, nicotinamide analogues strongly suppressed TPA-induced accumulation of inflammatory cells and vascular permeability, while epidermal hyperplasia was not significantly affected.
Article
Full-text available
The effects of nicotinamide in an abdominal island pedicle skin flap were examined. A 7 x 7 cm island pedicle skin flap ligating the left inferior neurovascular pedicle was created on 50 male Sprague Dawley rats (250-275 grams) that were divided into five groups. Animals received either 0.6 cc of saline or doses of nicotinamide for 16 days (14 days preoperatively and 2 days postoperatively): 25 mg b.i.d., 50 mg b.i.d., 100 mg b.i.d. or 200 mg b.i.d. Forty-eight hours postoperatively each animal received 25 mg of Fluorescein via the tail vein. The area of necrosis was visualized and quantified and is presented as % survival. A one factor Fisher PLSD test was performed with a statistical significance of p less than 0.05 with the results as follows: saline 58.8%, 25 mg 68.6%, 50 mg 82%, 100 mg 80.8%, and 200 mg 86%. From this data it would appear that the angiogenic factor nicotinamide may increase random flap survival.
Article
Full-text available
Nicotinamide can facilitate DNA repair by inhibiting poly(ADP-ribose) polymerase, increasing NAD levels and adjusting other related enzyme activities. This review will summarize recent work on the design of poly(ADP-ribose) polymerase inhibitors, poly(ADP-ribose) glycohydrolase inhibitors and will discuss the possible use of drugs that interact with NAD synthetic enzymes.
Article
Full-text available
1. Nicotinamide inhibits histamine release by antigen from chopped lung tissue of a sensitized guinea pig. Addition of succinate potentiates this histamine release and accompanying increase in oxygen uptake. However, nicotinamide, though it inhibits increased release of histamine, does not inhibit the increased uptake of oxygen.2. Histamine release from guinea pig lung by sinomenine, compound 48/80, and decylamine, whose action is not considered to involve enzymatic process, differing from that of antigen, is also inhibited by nicotinamide.3. Nicotinamide inhibits anaphylactic contraction of guinea pig ileum and, apparently weakens passive cutaneous anaphylaxis.4. Inhibition of anaphylactic histamine release and contraction of plain muscle by nicotinamide does not prevent desensitization. The plain muscle, from which nicotinamide had been washed off, is capable of undergoing contraction in response to the antigen. Consequently, nicotinamide does not inhibit the union of antigen and antibody.5. Nicotinamide analogs which are DPNase inhibitor, such as nicotinic acid, isonicotinic acid hydrazide, pyridine-3-sulfonic acid, and iproniazid, also inhibit histamine release by antigen in various degrees.6. There is no difference in DPNase activity between sensitized and unsensitized guinea pig lungs. Antigen does not cause any observable change in the DPNase activity of sensitized guinea pig lung. Partially purified bovine spleen DPNase does not increase the release of histamine in vitro, either from the chopped lung tissue of a guinea pig or from subcellular large granules of a dog liver.7. The result, of present series of experiments suggests that the inhibition of histamine release by nicotinamide in antigen-antibody reaction is not the result of inhibition of DPNase but rather is of a type that blocks linking of chemical stimulation, caused by antigen-antibody union, with allergic changes proceeding inside the cell, by a mechanism different from that of respiratory enzyme inhibitors.
Article
Background Ultraviolet (UV) radiation can profoundly suppress the cutaneous immune system, thus enhancing carcinogenesis. Agents that prevent UV-induced immunosuppression may thus reduce skin cancer. Nicotinamide (vitamin B3) prevents UV-induced immunosuppression and carcinogenesis in mice, and solar-simulated (ss) UV-induced immunosuppression in humans. Its effectiveness against different UV wavebands and mechanism of action is as yet unknown. Objectives To determine the effects and mechanisms of topical nicotinamide on UV-induced suppression of delayed type hypersensitivity (DTH) responses in humans. Methods Healthy Mantoux-positive volunteers in four randomised, double-blinded studies were irradiated with solar-simulated (ss)UV (UVB + UVA) or narrowband UVB (300 nm) or UVA (385 nm). Topical nicotinamide (0·2% or 5%) or its vehicle were applied immediately after each irradiation. Mantoux testing was performed at irradiated sites and adjacent unirradiated control sites 48 h after the first irradiation and measured 72 h later. Immunosuppression was calculated as the difference in Mantoux-induced erythema and induration at test sites compared to control sites. Human keratinocyte cell cultures, with and without ssUV and nicotinamide, were used for quantitative real-time reverse transcriptase-polymerase chain reaction assessment of TP53 and enzymes that regulate oxidative phosphorylation. Results Nicotinamide cooperated with ssUV to increase enzymes involved in cellular energy metabolism and p53, and significantly protected against immunosuppression caused by UVB, longwave UVA and single and repeated ssUV exposures. Conclusions Longwave UVA, which is poorly filtered by most sunscreens, was highly immune suppressive even at doses equivalent to 20 min of sun exposure. Nicotinamide, which protected against both UVB and UVA, is a promising agent for skin cancer prevention.
Article
Skin pigmentation is caused by various physical and chemical factors. It might also be influenced by changes in the physiological function of skin with aging. Nicotinamide adenine dinucleotide (NADH) dehydrogenase is an enzyme related to the mitochondrial electron transport system and plays a key role in cellular energy production. It has been reported that the functional decrease in this system causes Parkinson's disease. Another study reports that the amount of NADH dehydrogenase in heart and skeletal muscle decreases with aging. A similar decrease in the skin would probably affect its physiological function. However, no reports have examined the age-related change in levels of NADH dehydrogenase in human skin. In this study, we investigated this change and its effect on skin pigmentation using cultured human epidermal keratinocytes. The mRNA expression of NDUFA1, NDUFB7, and NDUFS2, subunits of NADH dehydrogenase, and its activity were significantly decreased in late passage keratinocytes compared to early passage cells. Conversely, the mRNA expression of melanocyte-stimulating cytokines, interleukin-1 alpha and endothelin 1, was increased in late passage cells. On the other hand, the inhibition of NADH dehydrogenase upregulated the mRNA expression of melanocyte-stimulating cytokines. Moreover, the level of NDUFB7 mRNA was lower in pigmented than in nonpigmented regions of skin in vivo. These results suggest the decrease in NADH dehydrogenase with aging to be involved in skin pigmentation.
Article
Kojic acid functions as an antioxidant in cosmetic products. Kojic acid was not a toxicant in acute, chronic, reproductive, and genotoxicity studies. While some animal data suggested tumor promotion and weak carcinogenicity, kojic acid is slowly absorbed into the circulation from human skin and likely would not reach the threshold at which these effects were seen. The available human sensitization data supported the safety of kojic acid at a use concentration of 2% in leave-on cosmetics. Kojic acid depigmented black guinea pig skin at a concentration of 4%, but this effect was not seen at 1%. The Cosmetic Ingredient Review (CIR) Expert Panel concluded that the 2 end points of concern, dermal sensitization and skin lightening, would not be seen at use concentrations below 1%; therefore, this ingredient is safe for use in cosmetic products up to that level.
Article
Calcipotriene has limited efficacy in treating psoriasis. By inhibiting proinflammatory cytokines such as interleukin-12, interleukin-23, and tumor necrosis factor-alfa, nicotinamide may enhance the efficacy of calcipotriene therapy when used in combination. We sought to determine if the combination of nicotinamide with calcipotriene is more effective than either component alone. In this randomized, double-blinded, multicenter 7-arm bilateral comparison-controlled trial, patients were randomized to two of 7 treatments--placebo, calcipotriene 0.005% alone, nicotinamide 1.4% alone, calcipotriene plus nicotinamide 0.05%, calcipotriene plus nicotinamide 0.1%, calcipotriene plus nicotinamide 0.7%, or calcipotriene plus nicotinamide 1.4%--each administered to lesions on one side of the body or to one of two lesions at least 5 cm apart, for 12 weeks. Efficacy was measured using a clear to almost clear outcome. In all, 50.0% of patients in the calcipotriene and nicotinamide 1.4% combination group achieved a clear to almost clear outcome at week 12, compared with only 18.8% of patients treated with placebo (P = .002), 25% of patients treated with nicotinamide 1.4% alone (P = .02), and 31.5% of patients treated with calcipotriene alone (P = .096). A dose-response trend existed for increasing concentrations of nicotinamide, but it was not significant. The relatively small patient numbers, relatively high placebo effect, and maximum in-life portion of only 12 weeks of dosing are weaknesses of the study. This study provides evidence that using the combination nicotinamide and calcipotriene may provide additional benefit in the topical treatment for patients with psoriasis and may be an adequate steroid-sparing substitute treatment.
Article
Tat is a multifunctional transactivator encoded by human immunodeficiency virus type 1 (HIV-1). Tat transactivating activity is controlled by nicotinamide adenine nucleotide(+) (NAD(+))-dependent deacetylase sirtuin 1 (SIRT1). Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the conversion of nicotinamide into NAD(+), which is crucial for SIRT1 activation. Thus, the effect of Nampt on Tat-regulated SIRT activity was studied in Hela-CD4-beta-gal (MAGI) cells. We demonstrated that Tat caused NAD(+) depletion and inhibited Nampt mRNA and protein expression in MAGI cells. Resveratrol reversed Tat-induced NAD(+) depletion and inhibition of Nampt mRNA and protein expression. Further investigation revealed that Tat-induced inhibition of SIRT1 activity was potentiated in Nampt-knockdown by Nampt siRNA compared to treatment with Tat alone. Nampt siRNA potentiated Tat-induced HIV-1 transactivation in MAGI cells. Altogether, these results indicate that Nampt is critical in the regulation of Tat-induced inhibition of SIRT1 activity and long terminal repeat (LTR) transactivation. Nampt/SIRT1 pathway could be a novel therapeutic tool for the treatment of HIV-1 infection.
Article
Sun protective measures can reduce numbers of both precancerous actinic keratoses and cutaneous squamous cell carcinomas within relatively short periods of time even in high-risk populations. Sunscreens, which tend to provide greater protection against shortwave UVB than against longer wavelength UVA radiation, can however provide only partial protection from the mutagenic and immune suppressive effects of sunlight. In large part, this reflects poor compliance with proper sunscreen application and reapplication. Skin cancer is by far the most common malignancy in Caucasian populations, and additional strategies to reduce the morbidity and economic burden of this disease are now urgently needed. Nicotinamide, the amide form of vitamin B3, is an inexpensive agent which is used for a variety of dermatological applications with little or no toxicity even at high doses. Nicotinamide has photoprotective effects against carcinogenesis and immune suppression in mice, and is photoimmunoprotective in humans when used as a lotion or orally. UV irradiation depletes keratinocytes of cellular energy and nicotinamide, which is a precursor of nicotinamide adenine dinucleotide, may act at least in part by providing energy repletion to irradiated cells.
Article
Topical niacinamide and N-acetyl glucosamine (NAG) each individually inhibit epidermal pigmentation in cell culture. In small clinical studies, niacinamide-containing and NAG-containing formulations reduced the appearance of hyperpigmentation. To assess the effect of a combination of niacinamide and NAG in a topical moisturizing formulation on irregular facial pigmentation, including specific detection of changes in colour features associated with melanin. This was a 10-week, double-blind, vehicle-controlled, full-face, parallel-group clinical study conducted in women aged 40-60 years. After a 2-week washout period, subjects used a daily regimen of either a morning sun protection factor (SPF) 15 sunscreen moisturizing lotion and evening moisturizing cream each containing 4% niacinamide + 2% NAG (test formulation; n = 101) or the SPF 15 lotion and cream vehicles (vehicle control; n = 101). Product-induced changes in apparent pigmentation were assessed by capturing digital photographic images of the women after 0, 4, 6 and 8 weeks of product use and evaluating the images by algorithm-based computer image analysis for coloured spot area fraction, by expert visual grading, and by chromophore-specific image analysis based on noncontact SIAscopy for melanin spot area fraction and melanin chromophore evenness. By all four measures, the niacinamide + NAG formulation regimen was significantly (P < 0.05) more effective than the vehicle control formulation regimen in reducing the detectable area of facial spots and the appearance of pigmentation. A formulation containing the combination of niacinamide + NAG reduced the appearance of irregular pigmentation including hypermelaninization, providing an effect beyond that achieved with SPF 15 sunscreen.
Article
Pathogenicity of fungi is connected with their ability to easily penetrate the host tissues, survive in the infected host organism and use the elements of the host tissues as nutrients. Hence, the co-occurrence of pathogenic properties with the high enzymatic activity, which is manifested through the production of various enzymes including extracellular enzymes, was observed. It can be expected that it is possible to decrease fungal pathogenicity by lowering their enzymatic activity. The aim of the study was to determine the effect of nicotinamide on enzymatic activity of the fungi, which are most frequently isolated in cases of skin infection. Enzymatic activity was analysed using 15 Candida albicans, 15 Trichophyton rubrum and 15 Trichophyton mentagrophytes strains. The strains used for the study were collected from the current diagnostic material. API ZYM tests were used in diagnostic analysis. MICs of nicotinamide were determined by the macrodilution method in liquid medium. In the case of Candida strains, the presence of nicotinamide in the broth had a significant effect on the decrease of enzymatic activity (P < 0.05) of esterase (C4), esterase lipase (C-8), valin-arylamidase, acid phosphatase and alpha-glycosydase. A considerably stronger effect of nicotinamide was observed in the case of dermatophytes (P < 0.005). Its action led to a decrease in the activity of all the enzymes under study except alpha-glucosidase produced by T. rubrum strains. Thus, nicotinamide exhibited biological activity towards C. albicans, T. rubrum and Trichophyton mentagrophytes, which resulted in a decrease in the activity of enzymes produced by the fungi.
Article
A molecular pathway requiring vitamin B3 increases the production of neutrophils (pages 151–158). These findings could lead to new ways to treat neutropenias, diseases involving low neutrophil counts.
Article
It has been suggested that topically applied nicotinamide and its metabolite N-methylnicotinamide (NMN(+)) might be useful agents for treatment of dermatological disorders such as acne vulgaris and rosacea. This study aimed to find out if the mechanism of these therapeutic effects depends on their vascular effects, by investigating if nicotinamide and NMN(+) are able to influence vascular permeability of the vessels in the skin on the back of Wistar rats. A dose-dependent increase in vascular permeability was seen in rats treated intradermally with nicotinamide and NMN(+). Interestingly, a significantly stronger effect of NMN(+) compared with nicotinamide was evident. Increased vascular permeability in rats treated with 0.5% NMN(+) ointment was seen. Moreover, indomethacin, a cyclo-oxygenase 1 and 2 inhibitor and N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, reduced the observed effects of nicotinamide and NMN(+). This study provides direct in vivo evidence that nicotinamide and its metabolite NMN(+) increase skin vascular permeability in rats by a mechanism that may involve NO and prostaglandins.
Article
Vitamins are a natural constituent of human skin and are part of a system of antioxidants that protect the skin from oxidative stress. There has been an increased interest in the use of natural antioxidants such as vitamins to help restore dermal antioxidant activity. Vitamins A, C, E, and B3 have been shown to have potent antioxidant and anti-inflammatory properties, but to achieve optimal effectiveness, products must be delivered in appropriate formulations. Products containing alpha-tocopherol (vitamin E), L-ascorbic acid (vitamin C), retinol (vitamin A), and niacinamide (vitamin B3), are effective for the treatment of photoaging. These compounds have also shown effectiveness in the treatment of inflammatory dermatoses, acne, and pigmentation disorders and wound healing. There is emerging evidence that combinations of vitamins have additive effects that provide enhanced efficacy compared with individual compounds.
The in vitro antigen-induced histamine release from mouse peritoneal mast cells actively sensitized with IgE antibodies was inhibited by nicotinamide. The drug was either given in vivo to the sensitized mice (once daily 100 mg/kg) for 7 days before an in vitro experiment or incubated in vitro (in concentrations 1-40 mM) with sensitized mast cells before an antigen challenge. The possible action of nicotinamide on the mechanisms involved in the regulation of antigen-induced histamine release from mast cells is discussed.
Article
Epidermal nicotinamide adenine dinucleotides were measured in subcorneal and basal epidermal layers in patients with psoriasis and in healthy controls during a 2-week period in which they were treated once a day with 0.15% dithranol in white petrolatum. Lowry's microtechniques utilizing enzymatic cycling were used. In the controls the total NAD contents decreased 25% during the treatment period. The total NADP content did not change, nor did the proportions of NADH and NADPH. In the psoriatic patients effects of the treatment were seen only in the epidermis of the lesions. Both the total NAD and NADP displayed an initial increase on the second day, followed by a steady decrease to the levels found in the non-involved skin. During the first week of treatment parakeratosis was still evident in the lesions. In spite of variation in the total NAD contents during this period, a significant reduction of the percentage of NADH was found. Concomitant with the appearance of an orthokeratotic horny layer, both NAD+ and NADH returned to normal. The percentage contribution of NADPH did not change during these events.
Article
Epidermal nicotinamide adenine dinucleotides were measured in subcorneal and basal epidermal layers in patients with psoriasis and neurodermatitis and in healthy controls. Lowry's microtechniques utilizing enzymatic cycling were used. The total NAD content in these groups was except for the involved psoriatic skin about 1.1 mmoles/kg dry weight. Between 40 to 50% of this content consisted of the reduced form. In the involved psoriatic skin the total NAD content was increased to 1.5 mmoles/kg, this increase being mainly due to a rise in NAD+. There was no difference in NAD content between epidermal layers in the various groups studied. The total NADP content was near 0.15 mmoles/kg in healthy controls and in patients with neurodermatitis. The subcorneal layers contained 10% more of the dinucleotide than the basal layers, but in the two layers the reduced form amounted to about 80% of the total. In both non-involved and involved skin of the psoriatic patients the total NADP content was significantly increased above the control level, by up to 20% in the former and up to 65% in the latter. In the two layers studied the NADP+ content was increased by about 75% in both non-involved and involved areas. In contrast, the NADPH content rose only in the basal layers of the lesion, by 55%. The increased levels of NADP+ and NADPH found in psoriasis might suggest an accelerated or differently conducted NADPH dependent biosynthesis in this disease.
Article
The major action of nicotinic acid appears to be a reduction in the synthesis of VLDL by the liver. This action likely arises both from decreased availability of fatty acid precursors, owing to the antilipolytic effect on adipose tissue, and specific inhibition of the synthesis of apo (B). Partial inhibition of cholesterol synthesis at HMG CoA reductase may also contribute to the decline in VLDL production. Decreased catabolism of apo A-I appears to account for the elevation of HDL and altered HDL subtype distribution. However, the molecular events responsible for these diverse actions of nicotinic acid in the hepatocyte remain to be determined. The realization that nicotinic acid has specific receptors on adipocytes and the success of the G-protein concept in explaining the antilipolytic action of this drug is a significant advance in niacin pharmacology. It seems likely that specific receptors for nicotinic acid may also be present on hepatocytes. Such receptors might interact with the hepatocyte G-protein system in a fashion similar to that characterized for adipocytes. Alternatively, nicotinic acid plasma membrane receptors may activate other signal transduction pathways in the hepatocyte such as calcium mobilization or phosphoinositide hydrolysis. Perhaps nicotinic acid receptor-ligand complexes modulate the expression of genes, such as for apo (B), in a manner similar to steroid hormone receptors. Clearly, many interesting cell and molecular biology problems remain to be investigated in the course of understanding the mechanism of action of nicotinic acid as an antihyperlipidemic drug. It is now appropriate to compare the antilipidemic action of nicotinic acid to that of other drugs. Nicotinic acid decreases the serum levels of both triglycerides and total cholesterol. It lowers serum levels of VLDL and LDL lipoproteins and raises the serum level of HDL. In particular, nicotinic acid raises the HDL2 fraction, which is considered to be beneficial in reverse cholesterol transport (69). This favorable pattern is shared by the HMG-CoA reductase inhibitor lovastatin, which has the advantage of a more effective cholesterol lowering effect: 20-35% compared to 10-15% for nicotinic acid (27, 44). Both agents can be used with bile acid sequestrants, cholestyramine, and colestipol to about double the cholesterol-lowering effect (73). Nicotinic acid has had the longest period of successful use as an antihyperlipidemic and was the only drug that demonstrated a decrease in mortality in the Coronary Drug Trial after a 15-year follow-up (15, 22). Thus, nicotinic acid still holds a first-line position in the treatment of the most common types of hyperlipidemia. Nicotinic acid is especially useful in patients with severe hypertriglyceridemia (type-V hyperlipoproteinemia). It remains to be seen if lovastatin with its smaller once-a-day dosage and less side actions will replace nicotinic acid; lovastatin has been in use for only about six years (73). The use of nicotinic acid as a vasodilator has been largely replaced by other therapy. Certainly there are enough analogues for this purpose, and further exploration would not appear to be fruitful. Other applications of nicotinic acid appear each year. None have proven of value although further explorations should not be discouraged. Nicotinamide has few uses as a drug. Its antidiabetic action prolongs the remission that follows the onset of type I (insulin-dependent) diabetes (77, 78). Immunosuppressive therapy with cyclosporine is currently used for this purpose (9). This activity of nicotinamide should certainly be further explored even though transplantation of beta cells now appears more feasible.
Article
We investigated the effects of nicotinamide and 3-aminobenzamide, known as inhibitors of poly (ADP-ribose) synthetase, on the expression of interferon- gamma (IFN-gamma)-induced class I and II major histocompatibility complex (MHC) molecules on the surface of cultured human umbilical vein endothelial cells (HUVEC) and human dermal fibroblasts (HDF). Indirect immunofluorescent staining on HUVEC and HDF was performed using monoclonal antibodies against class I MHC (HLA-A,B,C) and class II MHC (HLA-DR, HLA-DP and HLA-DQ) molecules, and then the expression of these molecules was determined using a fluorescence flow cytometry. Human recombinant IFN-gamma (100 U/ml) increased the expression of HLA-A,B,C molecules, and induced the expression of HLA-DR molecules and, to a lesser extent, of HLA-DP on both HUVEC and HDF. HLA-DQ molecules were not induced by IFN-gamma on either cell type. Nicotinamide and 3-aminobenzamide in the concentration greater than or equal to 1 mM reduced the IFN- gamma -induced expression of HLA-DR and HLA-DP on both HUVEC and HDF, whereas neither agent in the concentration of up to 10 mM affected the IFN- gamma -induced increase in HLA-A,B,C molecule expression. These data suggest that nicotinamide and 3-aminobenzamide suppress antigen presenting function of class II MHC positive endothelial cells and fibroblasts at the site of tissue inflammation.
Article
The antigen-induced release of histamine both in vitro from rat peritoneal cell suspensions containing mast cells actively sensitized with IgE antibody and in vivo from passively sensitized skin can be inhibited by relatively high doses of nicotinamide. The action of nicotinamide on the cellular mechanism involved in the regulation of antigen-induced histamine release is discussed.
The prior treatment of guinea pigs with nicotinamide diminished the symptoms of experimental bronchial asthma and the intensity of anaphylactic shock. Nicotinamide was also found to inhibit anaphylactic mast cell degranulation in mice and histamine release from rat-isolated peritoneal mast cells by compound 48/80. The role of nicotinamide in bronchial asthma is discussed.Copyright © 1974 S. Karger AG, Basel
Article
Unscheduled DNA synthesis of cultured hepatocytes in response to the direct acting carcinogen, methyl methanesulfonate, and to the procarcinogen, 2-acetylaminofluorene, was markedly increased when these cells were cultured in medium containing 25 mM nicotinamide. This effect of nicotinamide was apparently unrelated to the maintenance of intracellular nicotinamide coenzyme levels. The increase in unscheduled DNA synthesis mediated by 2-acetylaminofluorene in nicotinamide-treated hepatocytes could be partially accounted for by the maintenance of higher microsomal capacity for the metabolism of this procarcinogen. The ability of adult rat hepatocytes to respond to nicotinamide by increased unscheduled DNA synthesis was lost within a few hours after plating or upon short withdrawal of this vitamin from the culture medium.
Article
Nicotinamide stimulates the amount of DNA repair synthesis that occurs when freshly isolated, normal human lymphocytes are treated with UV irradiation, N-methyl-N′-nitro-N-nitroso guanidine, or dimethyl sulfate. Stimulation of DNA repair synthesis is concentration dependent and reaches a maximum between 2 to 5 mM nicotinamide. In contrast, DNA synthesis in cells that have not been subjected to DNA damage is not affected by nicotinamide at concentrations below 2 mM and is inhibited by concentrations between 2 to 5 mM. In the same concentration range, nicotinic acid has no effect on the rate of DNA synthesis in the presence or absence of DNA damage.
Article
Systemic and topical antimicrobials are effective in the treatment of inflammatory acne vulgaris; however, widespread use of these agents is becoming increasingly associated with the emergence of resistant pathogens raising concerns about microorganism resistance and highlighting the need for alternative nonantimicrobial agents for the treatment of acne. Nicotinamide gel provides potent antiinflammatory activity without the risk of inducing bacterial resistance. In our double-blind investigation, the safety and efficacy of topically applied 4% nicotinamide gel was compared to 1% clindamycin gel for the treatment of moderate inflammatory acne vulgaris. Seventy-six patients were randomly assigned to apply either 4% nicotinamide gel (n = 38) or 1% clindamycin gel (n = 38) twice daily for 8 weeks. Efficacy was evaluated at 4 and 8 weeks using a Physician's Global Evaluation, Acne Lesion Counts, and an Acne Severity Rating. After 8 weeks, both treatments produced comparable (P = 0.19) beneficial results in the Physician's Global Evaluation of Inflammatory Acne; 82% of the patients treated with nicotinamide gel and 68% treated with clindamycin gel were improved. Both treatments produced statistically similar reductions in acne lesions (papules/pustules; -60%, nicotinamide vs. -43%, clindamycin, P = 0.168), and acne severity (-52% nicotinamide group vs. -38% clindamycin group, P = 0.161). These data demonstrate that 4% nicotinamide gel is of comparable efficacy to 1% clindamycin gel in the treatment of acne vulgaris. Because topical clindamycin, like other antimicrobials, is associated with emergence of resistant microorganisms, nicotinamide gel is a desirable alternative treatment for acne vulgaris.
Article
Nicotinamide sensitizes murine tumours to the effect of radiation, but the pharmacokinetics are not well characterized at doses that are achievable in humans. In the mouse, nicotinamide given i.p. at doses of 100-500 mg/kg showed biphasic elimination with dose-dependent changes in half-life. The initial half-life increased significantly (P < 0.05) from 0.8 to 2 h and the terminal half-life increased from 3.4 to 5.6 h over the dose range studied. Clearance, however, decreased significantly from 0.3 to 0.24 l kg-1 h-1 only at the highest dose. Peak concentrations increased in a dose-dependent manner from 1,000 to 4,800 nmol/ml. The main plasma metabolite in the mouse is nicotinamide N-oxide, the peak concentration of which increased only from 80 to 160 nmol/ml. The N-oxide, which is also a weak radiosensitizer, is subject to reduction to the parent nicotinamide following administration at a dose of 276 mg/kg; peak concentrations of the N-oxide of 1900 nmol/ml were reached in 10 min, whereas concentrations of nicotinamide produced by reduction reached a maximum of 144 nmol/ml at 1 h. Elimination of the N-oxide was also biphasic, with initial and terminal half-lives being 0.39 and 1.8 h, respectively. The bioavailability of both drugs given via the i.p. as compared with the i.v. route was close to 100%. Tumour concentrations of nicotinamide paralleled those in the plasma after a short lag. Tumour nicotinamide adenine dinucleotide (NAD) concentrations were elevated by factors of 1.5 and 1.8 following doses of 100 and 500 mg/kg nicotinamide, respectively. Maximal concentrations were seen after 3-6 h, but levels remained elevated for 16 h. No change in tumour energy charge or in plasma 5-hydroxytryptamine was detected following a dose of 500 mg/kg nicotinamide.
Article
Nitric oxide (NO) exerts cytotoxic effects on various cells including neuronal cells. Glial NO production, mediated via induction of inducible NO synthase (iNOS), enhances neurotoxicity associated with the N-methyl-D-aspartate (NMDA) receptor. The present study examined whether nicotinamide, an inhibitor of poly (ADP-ribose) synthetase, inhibits NO formation in primary culture of rat glial cells. Nicotinamide (5-20 mM) suppressed iNOS mRNA expression and subsequent NO formation, which were induced by the combination of interferon-gamma and lipopolysaccharide, in a dose dependent manner. In addition, high-concentration (20 mM) nicotinamide decreased mRNA of interferon regulatory factor-1, a transcription factor which plays a major role in iNOS mRNA induction. These results suggest that nicotinamide may have protective effect on glial NO-related pathologies by preventing iNOS mRNA induction.