Vitamin B3 serves as a precursor to a family of endogenous enzyme co-factors, specifically nicotinamide adenine dinucleotide (NAD), its phosphorylated derivative (NADP), and their reduced forms (NADH, NADPH), which have antioxidant properties. These co-factors are involved in many enzymatic reactions in the skin, and thus have potential to influence many skin processes (14). This precursor role of vitamin B3 may thus be the mechanistic basis for the diversity of clinical effects observed for a material such as niacinamide. While precisely how the dinucleotide co-factors might contribute to all these effects has not been elucidated, several specific actions of niacinamide have been described (14-19). For example, topical niacinamide has the following effects:
• Niacinamide inhibits sebum production, specifically affecting the content of triglycerides and fatty acids. This may contribute to the observed reduction in skin pore size and thus improved skin texture (a component of texture being enlarged pores).
• Niacinamide increases epidermal production of skin barrier lipids (e. g., ceramides) and also skin barrier layer proteins and their precursors (keratin, involucrin, filaggrin), leading to the observed enhancement of barrier function as determined by reduced transepidermal water loss (TEWL). This improved barrier also increases skin resistance to environmental insult from damaging agents such as surfactant and solvent, leading to less irritation, inflammation, and skin redness (e. g., facial red blotchiness). Since inflammation is involved in development of skin aging problems, the barrier improvement may contribute to the anti-aging effects of topical niacinamide. The anti-inflammatory and sebum reduction effects of niacinamide likely contribute to the anti-acne effect reported for this material (20).
• Niacinamide and its metabolite 1-methyl nicotinate have been reported (21,22) to have anti-inflammatory properties (e. g., inhibition of inflammatory cytokines).
• Niacinamide increases production of collagen which may contribute to the observed reduction in the appearance of skin wrinkling.
• Niacinamide reduces the production of excess dermal GAGs (glycosaminogly – cans). In cell culture testing, as noted above for retinyl propionate, 0.5 mM niacinamide reduced excess GAG production by 15%.
• Niacinamide inhibits melanosome transfer from melanocytes to keratinocytes, leading to reduction in skin hyperpigmentation (e. g., hyperpigmented spots).
• Niacinamide inhibits skin yellowing. A contributing factor to yellowing is protein oxidation (glycation; Maillard reaction), which is a spontaneous oxidative reaction between protein and sugar (23-25), resulting in cross-linked proteins (Amedori products) that are yellow-brown in color. These products accumulate in matrix components such as collagen that have long biological half-lives (26,27). Niacinamide has been separately reported (28,29) to have anti-glycation effects.
Since nicotinic acid and its esters are also precursors to NAD(P), they would be expected to provide these same benefits to skin. Nicotinic acid and many (if not all) of its esters (following in-skin hydrolysis to free nicotinic acid) also stimulate blood flow, leading to increased skin redness or a flush response (30).