Nicotinamide (niacinamide), also known as vitamin B3, is the pyridine-3-carboxylic acid amide form of niacin. The water-soluble vitamin is not stored in the human body and must therefore be supplied externally. The study summarized below provides an overview of the mechanisms of action of niacinamide with a particular focus on its effect on the skin. Among other things, niacinamide is involved in cellular energy metabolism, DNA repair and the regulation of transcription processes.
Anti-acne effects of niacinamide
The anti-inflammatory and sebostatic properties of niacinamide justify its use as an active ingredient in topical formulations. In acne lesions, Propionobacterium acnes causes the production of IL-8, a chemokine that is mitogenically active in keratinocytes and is also involved in neutrophil chemotaxis. In acne lesions, activation of the transcription factors NF-κB (nuclear factor “kappa-light-chain-enhancer” of activated B cells) and activator protein 1 (AP-1) can also be observed. AP-1 is inhibited by niacinamide via poly(ADP-ribose) polymerase 1. In a randomized, double-blind control study of 160 participants with moderate and predominantly inflammatory acne, they were treated twice daily with a 45% niacinamide gel or a 4% erythromycin gel for a period of 8 weeks. Both groups of study participants reported a similar reduction in inflamed lesions, but those treated with 4% niacinamide gel had significantly greater improvements in seborrheic symptoms.
In another double-blind, placebo-controlled, randomized study of 130 participants, a moisturizer containing 2% niacinamide was found to significantly reduce the rate of sebum excretion compared to the placebo vehicle. A study by Shalita et al. reported a reduction in inflamed skin nodules in 82% of participants treated with 4% niacinamide for 8 weeks. Dos et al. report that 1% clindamycin phosphate and 4% niacinamide gel have the same efficacy in the treatment of moderate acne.
The role of niacinamide in atopic dermatitis
Moisturizers containing niacinamide have proven to be effective in the treatment of atopic dermatitis. In atopic dermatitis, there is a reduction in ceramides, an increase in transepidermal water loss (TEWL) and a damaged skin barrier. An in vitro study showed that niacinamide caused a two- to three-fold increase in free fatty acids and a one-and-a-half-fold increase in cholesterol. In atopic dermatitis, there is an increase in aquaporin, which codes for water-permeable channels, which in turn leads to increased water loss. This is prevented by niacinamide. In a study of 28 participants suffering from atopic dermatitis, niacinamide produced better results in reducing transepidermal water loss (TEWL) than white petrolatum. In a right-to-left comparison study conducted with 12 male participants with dry skin, 2% niacinamide applied twice weekly for 4 weeks reduced transepidermal water loss (TEWL) by 27% compared to the placebo vehicle and increased stratum corneum free fatty acids and ceramides by 67% and 34%, respectively. Another randomized control study included 292 participants who received 500 mg niacinamide twice daily versus placebo over a 12-month period. The results showed a consistent decrease in transepidermal water loss (TEWL) of 6-7% compared to the placebo applied to the face and limbs.
Anti-ageing effects of niacinamide
Niacinamide increases collagen production in fibroblast cultures and reduces the increased dermal glycoaminoglycosides in photodamaged skin. Niacinamide also increases the production of the epidermal proteins keratin, filaggerin and involucrin. The glycation between protein and sugar produces a yellowish coloration of the skin. Since niacinamide is a precursor of the antioxidant NADPH, it has anti-glycation properties and thus prevents the described coloration of the skin. In a double-blind, randomized, split-face control study involving 30 female participants, 5% niacinamide cream was compared with a pure vehicle cosmetic, which was applied to the face by the study participants over a period of 8 weeks. The use of niacinamide showed a significant reduction in wrinkling and skin roughness.
The role of niacinamide in autoimmune skin disorders
The mechanism of action behind the effect of niacinamide against vesiculobullous autoimmune diseases is thought to be its anti-inflammatory effect. Niacinamide inhibits cytokines such as IL-1β, IL-6, IL-8 or TNF. Bullous pemphigoid is one of the best documented and studied cases of niacinamide use. One case study reports efficacy in the treatment of localized bullous pemphigoid with daily application of 1.5 grams of niacinamide. In a double-blind control study with eight study participants suffering from pemphigus vulgaris, 60 lesions were randomly assigned to either 45 niacinamide gel or pacebo gel and then treated with the assigned gel for 30 days. It was found that the average epithelialization index was significantly higher for skin lesions treated with niacinamide. In addition, several case studies are available on successful applications of niacinamide and tetracycline in various autoimmune diseases with blistering, such as cicatricial pemphigoid, lichen planus pemphigoides, dermatitis herpetiformis and linear IgA dermatosis. As a result, niacinamide can be used to avoid the use of steroids.
Anticarcinogenic and photoprotective effects of niacinamide
The enzyme PARP-1, which is inhibited by niacinamide, is associated with cell senescence, ageing and cancer. Excessive activation of PARP-1 by UV radiation leads to depletion of cellular NAD, which in turn can cause glycolytic failure leading to cell necrosis. Niacinamide also regenerates cellular energy as it is a precursor of NAD and NADP. It also prevents the excessive activation of PARP-1 through negative feedback and thus prevents cell senescence. Niacinamide also protects against immunosuppression caused by UVA and UVB.
Conclusion
The underlying study concludes that the available literature and clinical data on niacinamide show that it is a well-tolerated active ingredient with positive effects in the treatment of various dermatological diseases due to its anti-inflammatory, anti-oxidative, protective and skin barrier repairing properties.
Underlying study:
Bains P, Kaur M, Kaur J, Sharma S.: Nicotinamide: Mechanism of action and indications in dermatology; in: Indian J Dermatol Venereol Leprol 2018;84:234-7