NIACINAMIDE

Niacinamide, an active form of vitamin B3, is recognised for its significant dermal benefits including skin brightening, anti-ageing properties and the protection of the skin barrier. Its widespread incorporation into cosmetic products, ranging from cleansers to serums, is attributed to its safety profile and proven efficacy. Recently, topical niacinamide has also been explored for other pharmaceutical applications, including skin cancers. Therefore, a fundamental understanding of the skin permeation behaviour of niacinamide becomes crucial for formulation design. Given the paucity of a comprehensive review on this aspect, we provide insights into the mechanisms of action of topically applied niacinamide and share the current strategies used to enhance its skin permeation. This review also consolidates clinical evidence of topical niacinamide for its cosmeceutical uses and as treatment for some skin disorders, including dermatitis, acne vulgaris and actinic keratosis. We also emphasise the current exploration and perspectives on the delivery designs of topical niacinamide, highlighting the potential development of formulations focused on enhancing skin permeation, particularly for clinical benefits.

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. 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, making skin healthier, brighter, and hydrated. 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.

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

Cutaneous hyperpigmentation occurs in multiple conditions. In addition, many Asian women desire a lighter skin colour. Thus, there is a need for the development of skin lightening agents. Niacinamide is a possible candidate. To investigate the effects of niacinamide on melanogenesis in vitro and on facial hyperpigmentation and skin colour in vivo in Japanese women. Melanin production was measured in a purified mushroom tyrosinase assay, cultured melanocytes, a keratinocyte/melanocyte coculture model, and a pigmented reconstructed epidermis (PREP) model. The clinical trials included 18 subjects with hyperpigmentation who used 5% niacinamide moisturizer and vehicle moisturizer in a paired design, and 120 subjects with facial tanning who were assigned to two of three treatments: vehicle, sunscreen and 2% niacinamide + sunscreen. Changes in facial hyperpigmentation and skin colour were objectively quantified by computer analysis and visual grading of high-resolution digital images of the face. Niacinamide had no effect on the catalytic activity of mushroom tyrosinase or on melanogenesis in cultured melanocytes. However, niacinamide gave 35-68% inhibition of melanosome transfer in the coculture model and reduced cutaneous pigmentation in the PREP model. In the clinical studies, niacinamide significantly decreased hyperpigmentation and increased skin lightness compared with vehicle alone after 4 weeks of use. The data suggest niacinamide is an effective skin lightening compound that works by inhibiting melanosome transfer from melanocytes to keratinocytes.

Nicotinamide (NAM), the amide form of vitamin B3, has gained increasing attention in dermatology due to its potential role in both skin aging and non-melanoma skin cancer (NMSC) prevention. This review summarizes the biological rationale and current clinical evidence supporting the use of NAM and other NAD + precursors in photoaging and cutaneous carcinogenesis. Chronic ultraviolet exposure induces DNA damage, oxidative stress, inflammation, immune dysregulation, and extracellular matrix remodeling, linking photoaged skin to increased susceptibility to actinic keratoses (AKs), squamous cell carcinoma (SCCs), and basal cell carcinoma (BCCs). Through the NAD + salvage pathway, NAM contributes to the maintenance of intracellular NAD + pools, thereby influencing energy metabolism, DNA repair, mitochondrial function, redox homeostasis, and the activity of NAD + -dependent enzymes. Preclinical studies indicate that NAM enhances DNA repair, reduces oxidative stress and inflammatory signaling, supports autophagy and mitophagy, and improves epidermal barrier function and extracellular matrix integrity. Clinically, the strongest evidence for anti-aging effects concerns topical NAM, which consistently improves wrinkles, texture irregularities, pigmentation, and barrier function. Oral NAM has demonstrated chemopreventive activity in high-risk patients with previous NMSC, particularly by reducing the incidence of new SCCs and AKs during active treatment. However, despite a strong mechanistic rationale, current evidence remains heterogeneous, and additional long-term, skin-focused clinical trials are needed to better define efficacy, safety, optimal dosing strategies, and patient selection.

A green digital image photometry method for the quantification of niacinamide in commercial cosmetic serums and creams is described. The method is based on the formation of an orange complex between niacinamide and iron (III) chloride in microplates under LED backlighting. The analytical signal was defined as (255 - B), where B corresponds to the blue channel intensity in the RGB colour model. Calibration was performed using microplate-based standards, and the method was applied to commercial cosmetic samples. Relative errors compared to HPLC-DAD were lower than 10.0%, and an elliptical joint confidence region test indicated no significant differences between slopes and intercepts and the ideal values of 1 and 0 at the 95% confidence level. Paired Student's t-test and F-test confirmed no significant differences in agreement and precision between methods. Deviations from labelled concentrations were generally below 6.0%, with a maximum value of 14.0%. Precision, evaluated over two months, showed relative standard deviations below 9.0%. Recovery values ranged from 84 to 114%. UV-Vis spectrophotometry was used to support the validation of the colorimetric response of the niacinamide-FeCl₃ system. The proposed approach was applied to rapid screening of niacinamide in cosmetic products and compared with a reference HPLC-DAD method.

Skin dullness, characterized by pigmentation disorders and yellowing, is a major cosmetic concern in Asian populations. Lipofuscin exhibits ultraviolet (UV)/visible light spectral absorption, reduces skin reflectance, and contributes to dullness, whereas existing therapies targeting melanogenesis and glycation lack comprehensive efficacy. This study aimed to evaluate the multimodal anti-dullness effects of a novel formulation (HNHT: hyaluronic acid, niacinamide, hydrolyzed red algae, and tranexamic acid). In vitro models (melanocytes, keratinocytes, fibroblasts, ex vivo skin model, and three-dimensional (3D) skin models) were used to assess melanin regulation, glycation inhibition, and lipofuscin clearance. In ultraviolet B (UVB)-exposed 3D skin models, 12.5% HNHT significantly improved skin color, appearance, and brightness (8.44% increase in L* value) and reduced melanin content (12.5% inhibition). Then, 12.5% HNHT downregulated the expression of key melanogenic genes (TYR and MITF; p < 0.001) in melanocytes and decreased UVB-induced α-melanocyte-stimulating hormone secretion in keratinocytes (2867.78 versus 3444.72 pg/mL; p < 0.05). The formulation enhanced melanosome clearance through autophagy activation (174% LC3-II increase, 80% GP100 reduction; p < 0.01) and boosted antioxidant capacity via Nrf2 activation and reactive oxygen species reduction (p < 0.05). In glycation, 50% HNHT upregulated anti-glycation enzymes (GLO1, GLO2, and GPX1) and reduced carboxymethyllysine (CML) by 23.16% in fibroblasts (p < 0.01), while 100% HNHT decreased CML by 34.93% in ex vivo skin model. Furthermore, 50% HNHT suppressed hydrogen peroxide-induced lipofuscin accumulation by 52.20% (p < 0.01). These findings highlight HNHT as a multitargeted therapeutic agent that alleviates skin dullness through melanogenesis inhibition, enhances melanosome degradation, suppresses glycation, mitigates oxidative stress, and promotes lipofuscin clearance, thereby establishing a novel therapeutic paradigm against solar radiation-induced hyperpigmentation and skin yellowing.

Xerosis cutis is characterized by impaired epidermal barrier function, increased transepidermal water loss (TEWL), reduced hydration, and symptoms such as pruritus. To evaluate the efficacy, tolerability, and subjective perception of a topical formulation containing panthenol, niacinamide, and dipotassium glycyrrhizate in improving skin hydration and barrier function in subjects with dry, sensitive skin. In this randomized, intra-individual, split-leg clinical trial, subjects with xerosis applied the test emollient twice daily for 28 days to one pretibial area. The contralateral leg remained untreated as control. Assessments were performed at baseline (T0), 30 min, 24 h, 48 h, day 7 and day 28. Primary outcomes were corneometric stratum corneum hydration and TEWL. Secondary outcomes included deep skin conductance ("deep moisturization"), desquamation index, surface microrelief regularity (SEr), scaliness (SEsc), dermatologist-rated clinical signs, and participant self-assessment. Thirty-five participants (31 women; mean age 47.3 ± 2.0 years) were included. Compared with baseline (hydration: 21.3 ± 1.0 c.u., 95% CI: 19.3-23.3; TEWL: 9.2 ± 0.3 g/h/m 2 , 95% CI: 8.6-9.8) and untreated control, the treated leg showed greater corneometric hydration at all time points: 66.2% (33.9 ± 1.4 c.u., 95% CI: 31.1-36.7) at day 7 and 74.1% (35.2 ± 1.2 c.u., 95% CI: 32.8-37.6) at day 28 (all p < 0.001). TEWL decreased by 11.3% (8.2 ± 0.2 g/h/m 2 , 95% CI: 7.8-8.6) and 13.5% (7.9 ± 0.2 g/h/m 2 , 95% CI: 7.5-8.3), respectively (all p < 0.05). Deep moisturization increased by 5.7% (39.5 ± 0.9 μS at day 7, 95% CI: 37.7-41.3) and 7.3% (41.1 ± 0.8 μS at day 28, 95% CI: 39.5-42.7) (p < 0.05). The desquamation index decreased by 13.0% (29.50% ± 1.67% at day 7, 95% CI: 26.1-32.9) and 15.8% (26.77% ± 1.25% at day 28, 95% CI: 24.2-29.3), SEr increased by 46.9% (3.38 ± 0.15 a.u. at day 7, 95% CI: 3.08-3.68) and 54.2% (3.47 ± 0.15 a.u. at day 28, 95% CI: 3.17-3.77), and SEsc decreased by 67.0% (0.81 ± 0.12 a.u. at day 7, 95% CI: 0.57-1.05) and 76.3% (0.51 ± 0.07 a.u. at day 28, 95% CI: 0.37-0.65), respectively (all p < 0.05). Dermatologist assessments at all time points showed significant clinical improvement in dryness and pruritus in all participants (p < 0.001). Complete resolution was observed in all participants according to the 5-point scale, though this may reflect a floor effect given mild baseline scores. The topical formulation appeared to be an effective and well-tolerated emollient; however, the absence of a vehicle control precludes attribution of effects specifically to the active ingredients. Patient-reported outcomes should be interpreted with caution due to the unblinded design.

Ti 3 C 2 T x MXene is a two-dimensional material with exceptional electrical conductivity, rendering them promising candidates as ink for printable skin biosensors. However, their susceptibility to oxidation under biologically relevant conditions and the consequences of oxidation on material properties remain unclear, posing challenges for practical applications. The skin is the barrier to the external environment. Its microenvironment, including sweat, may influence MXenes stability and behavior. Rigorous dermal safety assessment is therefore essential before MXenes widespread use. In this study, we systematically investigated the oxidation kinetics of Ti 3 C 2 T x MXenes with different flake sizes in biologically relevant solutions under varying temperatures and light exposure. Our results showed that oxidation was accelerated primarily by ionic strength and temperature. To prolong the lifetime of MXenes, we evaluated common antioxidant skincare ingredients vitamin E, niacinamide, and N-acetyl cysteine, finding that vitamin E significantly slowed oxidation in dispersions. To assess oxidation-dependent toxicity, we examined skin irritation and sensitization induced by freshly synthesized, partially oxidized, and fully oxidized MXenes. Accordingly, MXene dispersions were pre-incubated to obtain partially and fully oxidized samples. Oxidation was defined by the loss of the plasmonic band in the UV-Vis spectrum, a functional readout linked to conductivity, and thus relevant to the intended application of MXenes. Then, dermal toxicity was assessed using the KeratinoSens® assay and reconstituted human scaffold-free skin cultures. Across all oxidation states, Ti 3 C 2 T x MXenes did not induce statistically significant skin irritation or sensitization. Furthermore, cellular uptake and mechanistic insights were explored by using confocal Raman spectroscopy and flow cytometry, showing Ti 3 C 2 T x MXene internalization and reduction in intracellular reactive oxygen species level. Together, these findings reveal the oxidation behavior of Ti 3 C 2 T x MXenes, identify a practical strategy to extend their functional lifetime, and establish dermal safety profiles under potential application relevant conditions, providing key intermediate evidence for future safe and sustainable biomedical applications.

Addison's disease, or primary adrenal insufficiency, is a rare endocrine disorder characterized by deficient glucocorticoid and mineralocorticoid production, frequently associated with cutaneous hyperpigmentation due to chronic elevation of adrenocorticotropic hormone. Facial hyperpigmentation may persist despite adequate hormonal replacement, representing a therapeutic challenge with limited evidence to guide dermatologic management. We report the case of a 41-year-old female patient with an eight-year history of progressive hyperpigmentation affecting the face, hands, and oral mucosa. Physical examination revealed severe facial involvement with brown-violaceous macules and associated telangiectasias. The patient had a prior diagnosis of autoimmune ovarian failure in 2017 and was diagnosed with Addison's disease in 2020, receiving stable glucocorticoid replacement therapy. Histopathological evaluation demonstrated basal layer hyperpigmentation without interface dermatitis, consistent with endocrine-related pigmentation and overlapping melasma features. A multimodal therapeutic approach was implemented, including picosecond Nd:YAG laser therapy (approximately seven sessions at six- to eight-week intervals), oral tranexamic acid (250 mg twice daily), and a topical depigmenting regimen containing tranexamic acid, niacinamide, retinoids, and antioxidants. The patient demonstrated a significant reduction in modified Melasma Area and Severity Index score from 19.8 to 7.8 (60.6% reduction), along with a marked improvement in quality of life, as evidenced by a posttreatment Melasma Quality of Life Scale score of 20/70. This case highlights that persistent hyperpigmentation in Addison's disease may not fully resolve with endocrine treatment alone and may require adjunctive dermatologic interventions. A personalized, multimodal strategy targeting multiple pathogenic pathways, including melanogenesis, plasmin-mediated signaling, vascular factors, and dermal pigment deposition, can achieve significant improvement, even in patients with darker phototypes and long-standing disease. These findings underscore the importance of a multidisciplinary approach and suggest a potential role for combination therapies, including laser-based modalities, in managing complex pigmentary disorders associated with systemic conditions. Further studies are needed to establish standardized treatment protocols and evaluate long-term outcomes.

The main causes of skin aging include both intrinsic and extrinsic factors such as oxidative stress triggered by reactive oxygen species (ROS), modification of collagen and elastin by reactive carbonyl species (RCS), UV exposure, lifestyle habits and environmental pollutants. Skin aging is the most visible manifestation of senescence and is unavoidable. In particular, delaying age-related changes in facial appearance is a key objective for older adults. To address this issue, naturally occurring compounds including vitamin C, vitamin E, coenzyme Q10, resveratrol, niacinamide, carnosine, retinols (vitamin A derivatives), and hyaluronic acid are commonly used in commercially available anti-aging skincare products. These compounds are considered to be ROS and RCS scavengers or powerful humectant. This article describes a new multi-targeted anti-aging compounds for skin applications, composed of two functional moieties: one that neutralizes ROS and the other scavenges RCS. These compounds exhibit potent skin anti-aging properties, as demonstrated by their rapid and efficient scavenging of RCS, an ORAC value more than twice that of Trolox, and strong transition-metal-chelating activity.

This study evaluated the safety and effectiveness of HYDRAGEL A2, an injectable medical device containing hyaluronic acid (HA), polynucleotides (PN), and niacinamide, for improving facial skin quality. These ingredients are increasingly recognized for their synergistic effects in aesthetic medicine, with HA and PN providing hydration and skin support, and niacinamide offering anti-inflammatory and antioxidant properties. A prospective, open-label clinical investigation was conducted on 42 female subjects (mean age 45 ± 1 years, Fitzpatrick skin phototypes II-V) to assess skin elasticity, hydration, and mild skin depression correction following cheek area injections. Efficacy was measured using the Global Aesthetic Improvement Scale (GAIS), Antera 3D ® (texture), Cutometer ® (elasticity/firmness), Corneometer ® (hydration), and Dermascan ® (density/thickness) devices at baseline (D0), week 2 (W2/D14), and week 6 (W6/D42). GAIS values showed significant overall facial improvement ( p < 0.001) by both investigators and subjects, where 100% of subjects rated their appearance as improved immediately post-injection (D0), with sustained improvements at D42. Objective measurements revealed significant improvements in skin texture (reduced roughness), elasticity, firmness, hydration ( p < 0.001), density, and thickness, demonstrating the combined benefits of the HA, PN, and niacinamide blend. Injection site reactions, primarily mild and transient, were reported immediately post-injection. Investigators and subjects reported high satisfaction with the product's ease of use and aesthetic outcomes. Globally, HYDRAGEL A2, leveraging the established benefits of HA, PN, and niacinamide, was well-tolerated and effectively enhanced facial skin quality, demonstrating significant and sustained improvements in monitored skin parameters. The study concludes that this combination of ingredients, formulated in HYDRAGEL A2, provides a well-tolerated approach associated with improvements in skin quality.