Nicotinamide

Author: Anoma Ranaweera, Medical Writer, Auckland, New Zealand, 2012.


What is nicotinamide?

Nicotinamide, also known as niacinamide or nicotinic acid amide, is the water-soluble, active form of vitamin B3. It has been increasingly studied for many different indications in the field of dermatology but more research is needed to clarify its value.

Nicotinamide is naturally present in small quantities in yeast, lean meats, fish, nuts and legumes. It is also often added to cereals and other foods. Oral nicotinamide is available as 20-30 mg in multivitamin combinations, and on its own as inexpensive 500-mg tablets. It has also been incorportated in many topical agents including sunscreens and cosmetic agents.

What is nicotinamide used for?

Vitamin B3 is essential for good health; deficiency leads to a serious illness, pellagra. Oral nicotinamide can be used effectively to treat pellagra.

Nicotinamide used as a medicine may benefit the skin in several different ways. It has been reported to:

  • Have anti-inflammatory properties, which may be used for the treatment of bullous (blistering) diseases.
  • Effectively treat acne by its anti-inflammatory action and reducing sebum.
  • Improve skin barrier function through decreasing water loss through the epidermis (the outer skin layer) thus increasing skin hydration.
  • Improve the complexion, by improving the pigmentation, blotchiness and redness of ageing skin; it is used in a number of cosmeceutical products.
  • Reduce actinic keratoses and possibly reduce the risk of skin cancer.

How does nicotinamide work?

The broad clinical effects of nicotinamide may be explained by its role as:

  • a cellular energy precursor
  • a modulator of inflammatory cytokines
  • an inhibitor of the nuclear enzyme poly(adenosine diphosphate-ribose [ADP]) polymerase [PARP], which plays a significant role in DNA repair, maintenance of genomic stability, and cellular response to injury including inflammation and apoptosis (cell death).

Nicotinamide and tetracycline for bullous pemphigoid

The combination of oral nicotinamide and tetracycline appears to be a useful alternative to systemic steroids in the treatment of bullous pemphigoid. It is less toxic and safer than dapsone and/or prednisone.

In at least one open-labeled clinical trial comparing the combination of 500 mg of nicotinamide, three times daily, and 500 mg of tetracycline four times daily, with prednisone therapy, in 20 patients with bullous pemphigoid, there were five complete responses and five partial responses, in the nicotinamide and tetracycline group compared with one complete response and five partial responses in the prednisone group, after 8 weeks of treatment. All five complete response patients in the nicotinamide and tetracycline group remained disease-free during medication tapering over a 10-month follow-up period, while three patients in the prednisone group had repeated disease flare-ups with steroid tapering during the same period of time.

Nicotinamide for dermatitis herpetiformis and linear IgA bullous dermatosis

The combination of tetracycline and nicotinamide has been used with varying degrees of success in the treatment of dermatitis herpetiformis, and linear IgA bullous dermatosis.

Nicotinamide for acne

Nicotinamide, available in topical cream, gel and oral forms (e.g. trade name Nicomide), has been shown to be effective in clearing acne. In a controlled clinical trial, 4% nicotinamide gel was found to be as effective as the topical antibiotic 1% clindamycin gel in the treatment of acne vulgaris in 76 patients with moderate acne. The study concluded that the anti-inflammatory properties of nicotinamide may have contributed towards its success in acne.

Nicotinamide also reduces facial sebum production. Sebum is responsible for facial shine and contributes to noninflamed comedones and inflammatory acne lesions. Results of a well-controlled clinical trial in Caucasian and Japanese women have shown that application of 2% nicotinamide moisturiser to the face for 4-6 weeks reduces sebum production with significant differences in facial shine and oiliness.

Nicotinamide gel is marketed as an over-the-counter treatment for acne in Canada, Australia, NZ, UK, USA and Ireland. If twice daily application causes excessive drying of the skin, one may reduce to one application a day, or every other day.

Nicotinamide is not recommended for acne in pregnant and nursing women.

Nicotinamide for rosacea

The clinical signs and symptoms of rosacea include increased facial skin dryness, redness and sensitivity. In at least two studies, moisturisers containing nicotinamide have been shown to improve skin barrier function in rosacea patients, leading to diminished reaction to irritants including cleansers and cosmetics.

Nicotinamide in anti-ageing skin care

Nicotinamide serves as a precursor of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are co-enzymes (facilitators of enzymatic reactions) essential for numerous metabolic pathways. These co-enzymes play a key role in the metabolism of glucose, cellular energy production, and synthesis of lipids. The levels of NADH / NADPH (the reduced forms of NAD and NADP) decrease with age, and topical nicotinamide appears to reverse the decline.

In multiple clinical studies, topical nicotinamide improved fine lines and wrinkles, hyperpigmented spots, red blotchiness, and skin sallowness (yellowing) as well as elasticity. One study showed nicotinamide to increase the skin's production of ceramides, which are natural emollients and skin protectants, thus improving skin hydration.

A double-blind, placebo-controlled, split-face, left-right, randomised 12-week study in 50 women evaluated the effects of 5% topical nicotinamide on various signs of skin aging. The researchers reported topical nicotinamide resulted in significant improvement in fine lines/wrinkles, pigmentation, texture and red blotchiness. The study was sponsored by Proctor and Gamble.

Another study of 30 healthy Japanese females reported improvement of eyelid wrinkles after 8 weeks of application of a cosmetic containing 4% nicotinamide.

Nicotinamide is well tolerated and often can be used by those who cannot tolerate topical retinoids or fruit acids.

Anticancer effects of nicotinamide

Ultraviolet radiation (UVR) is a major risk factor for skin cancer development. The mechanisms by which UVR leads to cancer are complex including direct damage to DNA and effects on the immune system. Nicotinamide has been shown to enhance the repair of direct and oxidative DNA damage in human keratinocytes and in human skin. It has potential to prevent UV-induced immune suppression. This was shown in a study of volunteers with a positive Mantoux test (positive tuberculin sensitivity test). The Mantoux reaction can be suppressed by exposure to UVR. Nicotinamide reduced this immune suppression when it was applied either before or after exposure to UVR (simulating normal sunlight exposure).

In a randomised controlled clinical trial in 50 patients, 1% nicotinamide gel applied twice daily to the head, forearms and hands for 6 months reduced the mean number of precancerous actinic keratoses by 28%. Another study has shown that oral nicotinamide also reduces the numbers of actinic keratoses compared to placebo. A reduction in skin cancers has also been observed in high-risk sun-damaged patients treated with nicotinamide.

Nicotinamide does not work as a sunscreen (and does not prevent sunburn). It does not have antioxidant properties, but it may affect the complement cascade, cell energy metabolism, and apoptosis (cell death).

Adverse effects of oral nicotinamide

Oral nicotinamide is generally well tolerated in doses under 3 g/day. It does not cause flushing or gastrointestinal upset, unlike its precursor nicotinic acid. It has been reported to increase sweating, to raise blood sugar, and to cause hypotension.

Very high doses of nicotinamide may lead to nausea.

New Zealand approved datasheets are the official source of information for these prescription medicines, including approved uses and risk information. Check the individual New Zealand datasheet on the Medsafe website.

 

Related Information

References

  • Damian DL, Patterson CRS, Stapelberg M, Park J, Barnetson RS, Halliday GM. UV radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide. J Invest Dermatol 2008; 128: 447–454. PubMed
  • Kolbach DN, Remme JJ, Bos WH, Jonkman ME, De Jong MCJM, Pas HH, Van Der Meer JB. Bullous pemphigoid successfully controlled by tetracycline and nicotinamide. Br J Dermatol 1995; 133: 88–90. PubMed
  • Kim B, Halliday GM, Damian DL. Oral nicotinamide and actinic keratosis: a supplement success story. Curr Probl Dermatol 2015; 46: 143–9. DOI: 10.1159/000366550. PubMed
  • Draelos ZD, Matsubara A, Zhuang J, et al. The effect of 2% niacinamide on facial sebum production. J Cosmet  Laser Ther 2006; 8: 96–101. PubMed
  • Bissett DL, Oblong JB, Berge CA. Niacinamide: A B vitamin that improves aging facial skin appearance. Dermatol Surg 2005; 31: 860–5. PubMed
  • Hakozaki T; Minwalla L; Zhuang J, et al. The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. Br J Dermatol 2002; 147: 20–31. PubMed
  • Surjana D, Halliday GM, Damian DL. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin. Carcinogenesis 2013; 34: 1144–9. DOI: 10.1093/carcin/bgt017. PubMed
  • Surjana D, Halliday GM, Martin AJ, Moloney FJ, Damian DL. Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials. J Invest Dermatol 2012; 132: 1497–500. Journal
  • Vitamin B derivative reduces risk for further skin cancer. Medscape Conference News

On DermNet NZ

Other websites

Books

See the DermNet NZ bookstore