Summary and Key Features
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Niacinamide, or vitamin B 3 , is a water-soluble, relatively stable, low-molecular-weight vitamin that readily penetrates the stratum corneum.
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Niacinamide has been used topically in prevention of photodamage, reduction in acne, improvement in bullous pemphigoid, and treatment of rosacea and atopy.
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Panthenol, or provitamin B 5 , is also known as pantothenol and pantothenyl alcohol.
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Panthenol has been used topically to treat wounds, bruises, scars, pressure and dermal ulcers, thermal burns, postoperative incisions/distention, and dermatoses.
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Topical vitamin B 3 and provitamin B 5 provide a variety of beneficial effects to skin, such as barrier enhancement, moisturization, and improvement in the appearance of aging skin.
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NAD+ and related precursors, such as niacinamide, have found specific and novel mechanistic linkages to aging diseases.
Introduction
The nutritional value of B vitamins has long been known, and in recent years the utility of topical vitamin B 3 (niacinamide, nicotinamide) and provitamin B 5 (panthenol) is being increasingly recognized. Niacinamide is the amide version of niacin (nicotinic acid), the latter of which has flushing effects when topically applied and will not be discussed in this review. There are several reports of topical niacinamide and panthenol providing therapeutic dermatologic effects. More recently, both of these B vitamins have been utilized in topical cosmetic products to provide beneficial effects for a wide array of more common skin problems such as those associated with aging. In those applications, these B vitamins have been found to be well tolerated by the skin and can thus be used broadly across skin types.
The likely mechanisms involved in having these effects have not been completely elucidated. However, since both of these B vitamins are precursors to important cofactors in metabolism, it is probable that there is a general mechanistic effect on bioenergetics and cellular homeostasis.
This chapter overviews the topical effects and mechanisms of these B vitamins. Since there is considerable literature on both materials, this review can by necessity only briefly describe the array of published work.
Niacinamide
Material
Vitamin B 3 encompasses a family of structurally similar compounds. The focus here is on niacinamide, also known as nicotinamide and, in older literature, vitamin PP (for pellagra preventing). Niacinamide is a water-soluble, stable, low-molecular-weight substance that readily penetrates the stratum corneum. Mechanistically, it is a precursor that rapidly incorporates into the NAD(P)H pools, which serve as critical redox factors in numerous enzymatic reactions. More recently, NAD+ has been shown to have significant roles in regulating cellular metabolism via protecting cells from oxidative stress and as a function of aging. This is of particular relevance to skin that is exposed daily to environmental stressors such as ultraviolet (UV) light, pollution, and smoke, since it has been reported that NAD+ levels are lower in aged skin in both genders.
Topical Therapeutic Effects
Niacinamide has been used topically in prevention of photodamage, reduction in acne, improvement in bullous pemphigoid, and treatment of rosacea and atopy. The specific mechanisms for these effects have not been defined, although there are considerable effects of niacinamide that may contribute. Additionally, niacinamide is a precursor to NAD(P) and their reduced forms NAD(P)H, cofactors that are important in many cellular metabolic enzyme reactions, so it has potential to impact many tissue functions. Also, since the reduced forms of these cofactors are potent antioxidants, a redox regulation mechanism is a strong possibility. Clinical studies have found that topical niacinamide is able to reduce the incidence of actinic keratosis in both males and females.
Topical Cosmetic Effects
Topical niacinamide is extremely well tolerated by the skin. That mildness and the broad use potential noted earlier have triggered several recent controlled cosmeceutical clinical studies, which have revealed many beneficial effects of chronic topical niacinamide in aging skin.
Barrier and Irritation
Topical niacinamide reduced transepidermal water loss (TEWL), indicating improved barrier function. The treated skin was found to be significantly more resistant to damage by barrier-destructive agents such as the surfactant sodium lauryl sulfate (SLS) and trans -retinoic acid. This translates into less irritation and less red blotchiness in the face ( Fig. 6.1 ).
The mechanism for barrier improvement is likely due to niacinamide-induced increases in skin barrier layer lipids such as ceramides and barrier layer proteins such as keratin, involucrin, and filaggrin. Increases in these primary structural components would be expected to have a significant effect on building the barrier.
Hyperpigmented Spots
Chronic topical niacinamide also reduces the appearance of hyperpigmented spots in both Caucasian and Asian facial skin. The mechanism for this was found to involve inhibition of melanosome transfer from the melanocytes to the keratinocytes. With transfer inhibited, the melanocytes stop producing melanin. As anticipated, the melanin reduction effect is reversible with cessation of niacinamide treatment both in culture and clinically.
Yellowing (Sallowness)
With topical niacinamide, yellowing was significantly prevented ( Figs 6.2 and 6.3 ). The mechanism for this may involve antioxidancy via NAD(P)H, specifically prevention of protein glycation (Maillard reaction), the end products of which are cross-linked yellow-brown proteins (Amadori products) that accumulate in skin. Niacinamide has been reported to have antiglycation properties.
Texture and Sebum
A factor in poor texture of older skin is enlarged pore size. Topical niacinamide has been observed to significantly improve texture with chronic usage. Niacinamide reduces sebum production, which may lead to reduction in pore size and thus smoother texture.
Environmental Protection
Treatment with topical niacinamide has been found to significantly prevent and reduce the level of erythema induced by solar simulated light. This included a reduction in redness as well as corollary reduction in inflammatory biomarkers detected from the skin’s surface.
Wrinkles
Chronic topical niacinamide treatment has been shown to have a significant effect on reducing fine lines and wrinkles, albeit relatively small in magnitude ( Fig. 6.4 ). There are two mechanisms that have been explored regarding this wrinkle reduction: an increase in dermal collagen production and a decrease in excess upper dermal glycosaminoglycan (GAG) production. While a low level of GAG is required for normal structure and function of the dermal matrix, excess levels are associated with poor visible appearance of skin.
