The anti-aging effects of niacinamide

Patti Farris, M.D.Pellagra is a vitamin deficiency caused by a lack of cellular niacin or its precursor tryptophan. First described for its dermatological symptoms by Gaspar Casal in Spain, Pellagra is characterized by dermatitis, diarrhea and dementia and can be seen in children with malabsorption, adolescents with anorexia nervosa or in patients with chronic alcoholism. The skin lesions in this vitamin deficiency are triggered by sun exposure and appear on the face, neck and extremities.  The eruption presents as a marginated erythema with scaling or blisters. Casal’s necklace is a broad collarette seen around the neck in patients with pellagra and is pathognomonic for this condition. It is through the study of patients with niacin deficiency that we have gained an understanding of the importance of vitamin B and its precursors for skin health.

Vitamin PP

Niacinamide (nicotinamide) or vitamin B₃ is a water-soluble amide of nicotinic acid historically referred to as vitamin PP for its ability to prevent pellagra. It is a precursor for co-factors NAD(H)and NADP(H) that are important in a variety of cellular pathways that affect skin physiology. NADH and NADPH decrease with age giving rise to the notion that supplementing skin with niacinamide can provide anti-aging benefits. In their reduced forms, NADH and NADPH act as antioxidants that can mitigate oxidative stress associated with intrinsic aging and photoaging.  Additionally, niacinamide stimulates keratinocyte differentiation, believed to be a result of increased intracellular NADPH.  Niacinamide has broad anti-inflammatory activity.  It inhibits nuclear factor kappa B (Nf-kB), reduces production of a variety of inflammatory cytokines, like IL-1 and IL-12, prevents degranulation of mast cells and inhibits leukocyte migration into the skin.

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Both oral and topical forms of niacinamide have been used to treat inflammatory skin conditions.  Nicotinamide has been used in combination with tetracycline for treating bullous pemphigoid. In a comparative study, 2g/day tetracycline plus 1.5g/day of nicotinamide performed equal to prednisone therapy offering a steroid-free option for BP patients. Topical niacinamide has been studied alone and in combination with calcipotriene for the treatment of patients with psoriasis.  Fifty percent of the combined group achieved total or nearly total clearing by week 12, while only 25% of those treated with 1.4% niacinamide alone and 31.5% treated with calcipotriene alone showed a response.  The authors suggest that topical niacinamide may provide additional benefits and be useful as a steroid-sparing substitute.  

NEXT: Cosmeceutical use

Cosmeceutical use

Niacinamide has become popular as a cosmeceutical ingredient. Cosmeceuticals contain three primary forms of vitamin B₃ including niacinamide, nicotinic acid and nicotinate esters. Niacinamide is the most well studied form of topical B₃ and is generally regarded as the most efficacious.  Niacinamide readily penetrates the stratum corneum and has a favorable tolerability profile, as it does not cause cutaneous irritation or flushing commonly seen with nicotinic acid. It can be used in formulations, at concentrations up to 5%, with a very low incidence of irritation. On the other hand, nicotinic acid causes vasodilation and redness, making it less desirable as a topical ingredient.

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One of the unique benefits of niacinamide as an anti-aging ingredient is that it enhances barrier function.  NADPH is a cofactor for the synthesis of fatty acids and lipids, such as ceramides, that are crucial for epidermal barrier function. In addition, niacinamide increases the production of proteins such as keratin, involucrin and filaggrin that are important factors in the formation and maintenance of the cornified envelop (or outermost layer of the skin).  Barrier compromise is common in aging skin and can contribute to heightened sensitivity and irritation by allowing external insults easier entry into the skin. Studies have demonstrated that topical application of niacinamide reduces skin sensitivity to irritating surfactants such as sodium laurel sulfate (SLS) and can be used to improve the tolerability of ingredients such as retinoids.

NEXT: Photoaging agent

Photoaging agent

Niacinamide can be used to improve a variety of clinical stigmata seen in photoaging.  It is well known for its skin lightening properties by acting as both a tyrosinase inhibitor and preventing the transfer of melanosomes to keratinocytes, a property that is most remarkable at higher concentrations. Niacinamide inhibits protein glycation effectively reducing deposition of cross-linked collagen and elastin molecules in the skin. Cross-linked collagen and elastin molecules are stiff and rigid, resulting in altered viscoelastic properties of the skin. Skin sallowness seen in actinically damaged skin is believed to be a result of glycated cross-linked yellow-brown proteins that accumulate in the skin after sun exposure. Thus it is not surprising that topical application of niacinamide reduces skin sallowness. Topical niacinamide reduces fine lines and wrinkles after prolonged use. A 12-week clinical study of a topical 5% niacinamide emulsion demonstrated a 21% improvement in fine lines along with a 14% skin tone clarity and 15% radiance improvement. Although the mechanisms in play remain to be elucidated, in vitro studies suggest that niacinamide increases dermal collagen production while at the same time reducing excess dermal glycosaminoglycan production. Niacinamide also reduces facial sebum production making it a valuable ingredient for patients who desire skin rejuvenation, but may be acne-prone. The anti-inflammatory properties of niacinamide are also beneficial for acne-prone skin, especially in those patients with papules and pustules. Clinically it reduces pore size and improves skin texture.

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Oral and topical niacinamide have been shown to reduce UV-induced immunosuppression. Oral niacinamide reduces the onset of actinic keratosis, indicating that this vitamin may be helpful in reducing more terminal forms of photoaging including skin cancer formation.  Further studies are needed to determine if topical niacinamide can provide similar benefits.

Disclosures: Dr. Farris is a consultant to L’Oreal.

References

1.    Bissett DL, Oblong JE, Saud A, et al. Topical niacinamide provides skin aging appearance benefits while enancing barrier function. In: Elsner P, Maibach HI. (Eds,) Cosmeceuticals and Active Cosmetics, 2^nd edn. New York: Taylor & Francis Group, 2005,421-440.

2.    Ungerstedt JS, Blomback M, Soderstom T. Nicotinamide is a potent inhibitor of proinflammatory cytokines. Clin Exp Immunol 2003;131:48-52Fivenson DP, Breeman DL, Rosen GB, et al. Nicotinamide and tetracycline therapy of bullous pemphigoid. Arch Dermatol. 1994;130960;753-758

3.    Levine D, Even-Chen Z, Lipets I, et al. Pilot, multicenter, double-blind, randomized placebo-controlled bilateral comparative study of a combination of calcipotriene and nicotinamide for treatment of psoriasis. J Am Acad Dermatol 2010;63(5):775-81

4.    Draelos ZD, ERtel KD, Berge CA. Niacinamide-containing facial moisturizers improves skin barrier and benefits subjects with rosacea. Cutis 2005;776:135-141.

5.    Hakozaki T, Minwalla, Zhuang J, et al. The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. Br J Dermatol 2002;147:20-31.

6.    Greatens A, et al. Effective inhibition of melanosome transfer to keratinocytes by lectins and niacinamide is reversible. Exp Dermatol 2005;14(7):498-508.

7.    Matts PJ, Oblong JE, Bissett DL. A review of the range of effects of niacinamide in human skin. Int Fed Soc Cosmet Chem Mag 2002;5:285-289.

8.    Yatskay M, Du A, Chen N, et al. Poster presented at 23^rd World Congress of Dermatology, 2015 June 8-13 Vancouver, Canada.

9.    Sivapirabu G, Yiasemides E, Halliday GM et al. Topical nicotinamide modulates cellular energy metabolism and provides broad-spectrum protection against ultraviolet radiation-induced immunosuppression in humans. Br J Dermatol 2009;161:1357-1364.

10. Surjana D, Halliday GM, Maartin AJ, et al. Oral nicotinamide reduces actinic keratosis in phase II double-blinded randomized controlled trials. J Inves Dermatol 2012;132:1497-1500.