The skin barrier biochemical mechanisms responsible for defence against endogenous and exogenous damaging agents have been widely researched (1-3). These studies evidenced the fundamental role played by niacin (nicotinic acid or vitamin B3), a precursor of the coenzyme NAD+ (nicotinamide adenine dinucleotide). NAD+ is essential to all cellular processes involved in immune response and repairing DNA damage caused by UV radiation or aggressive chemicals. Niacin deficiency and consequent lack of NAD+ in keratinocytes causes intracellular incidents which can lead to lipid peroxidation, oxidative stress of the cell membranes, premature skin ageing, erythema and skin irritation, and eventually more serious consequences, including unrepaired DNA damage, disruption of epidermal barrier integrity, mutagenesis, immune suppression, actinic keratosis and skin cancers. The effects of menthyl nicotinate, a lipophilic derivative of niacin designed to deliver niacin to skin without causing irritation or excessive vasodilation, have been studied through in vitro testing on human keratinocyte cultures, to evaluate its anti-oxidant, anti-pollution, detox, protective efficacy against four damaging agents (UV radiation, oxidizing agents, urban dust and synthetic smoke). Menthyl nicotinate is capable of rapidly penetrating the skin barrier, hydrolysing on contact with skin esterases, releasing niacin in the underlying cutaneous layers and so activating NAD+ defence and repair activities. All tests indicate that menthyl nicotinate enhances cellular metabolism, protection and barrier function in skin against all four damaging agents. These scientific results are of great interest for cosmetic applications to sustain efficacy claims as anti-pollution, anti-aging, anti-free radicals, sun protection, and hair loss prevention.