Review

Skin Pharmacol Physiol 2014;27:311–315 Received: January 7, 2013

Accepted after revision: January 21, 2014
DOI: 10.1159/000359974
Published online: June 27, 2014

Niacinamide – Mechanisms of Action and

Its Topical Use in Dermatology
Johannes Wohlrab a, b Daniela Kreft a
a
Department of Dermatology and Venereology and b Institute of Applied Dermatopharmacy, Martin Luther
University Halle-Wittenberg, Halle (Saale), Germany

Key Words has the same vitamin activity as its amide [1]. After the
Niacinamide discovery of its ‘pellagra-preventing’ effect, nicotinic acid
amide has also been named vitamin PP or PP factor. It
exists either in the form of white crystalline powder or of
Abstract colourless crystals. It is odourless and has a salty, bitter
Niacinamide, an amide of vitamin B3 (niacin), is a hydrophilic taste [2]. The melting point is specified as 128–131 ° C, the
endogenous substance. Its effects after epicutaneous appli- pKa value as 3.3 (20 ° C) and the pH as 6.0–7.5 (β = 5 g/100
cation have long been described in the literature. Given a ml H2O) [2]. Niacinamide is a water-soluble vitamin. Its
sufficient bioavailability, niacinamide has antipruritic, anti- molar weight is 122.12 g/mol [3]. Today, niacinamide is
microbial, vasoactive, photo-protective, sebostatic and produced solely synthetically. Three different methods
lightening effects depending on its concentration. Within a are available: (1) oxidation of 3-ethyl-6-methylpyridine
complex metabolic system niacinamide controls the NFκB- and HNO3 into nicotinic acid which is then transformed
mediated transcription of signalling molecules by inhibiting with NH3 to nicotinic acid amide; (2) aminolysis of meth-
the nuclear poly (ADP-ribose) polymerase-1 (PARP-1). Nia- yl nicotinate and gaseous NH3, and (3) ammoxidation of
cinamide is a well-tolerated and safe substance often used 3-methylpyridine into cyanpyridine that is then partially
in cosmetics. Clinical data for its therapeutic use in various saponified into nicotinamide [4–6].
dermatoses can increasingly be found in the literature. Al-
though the existing data are not sufficient for a scientifically
founded evaluation, it can be stated that the use of niacina- Physiological Chemistry
mide in galenic preparations for epicutaneous application
offers most interesting prospects. © 2014 S. Karger AG, Basel Niacinamide can be found in free as well as in bound
form in plants and animal tissue, primarily as part of the
pyridine nucleotides nicotinamide-adenine dinucleotide
(NAD) and nicotinamide-adenine dinucleotide phos-
Introduction phate (NADP). It is ingested with food [7–9]. Approxi-
mately 500 ppm can be detected in yeast, between 10 and
Niacinamide (synonyms: nicotinamide, nicotinic acid 100 ppm in various bacteria, alfalfa, oat, maize, wheat,
amide, 3-pyridinecarboxamide) is part of the vitamin B palm kernel oil, soya beans, molasses, and in animal or-
group. It is converted in vivo from nicotinic acid, which gans like liver, kidneys and muscles [10–12]. After the
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© 2014 S. Karger AG, Basel Johannes Wohlrab, MD

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1660–5527/14/0276–0311$39.50/0 Department of Dermatology and Venereology

Martin Luther University Halle-Wittenberg
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E-Mail karger@[Link]
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co-enzymes have separated, niacinamide is resorbed al-
most completely in the small intestine [13]. Since resorp-
tion of niacinamide in concentrations between 250 and
1,200 mg does not reach a maximum and is not depen-
dent on the presence of sodium ions, it is assumed that
facilitated diffusion works as a means of transport [4]. Antimicrobial Ceramide synthesis
effects
After resorption niacinamide is stored as NAD in the liv-
er, thus the homoeostasis of the niacinamide in serum is
regulated [8]. Niacinamide is excreted through the kid-
neys [9]. Depending on the dose, different metabolites are
excreted [14].
Inhibition of Capillary permeability
melanosome Inhibition of
transfer nitric oxide
Biological Effects with Dermatological Relevance

Since niacinamide is essentially involved in the cellular

energy metabolism, the regulation of DNA synthesis, as
well as in transcription processes, various biological ef-
fects can be observed after in vitro and in vivo substitu- Sebostatic effect Anti-inflammatory
effects
tion [15–18]. These effects are particularly striking in
quantities that exceed physiological concentration, as
they can be reached by epicutaneous application of nia- Fig. 1. Overview of all dermatologically relevant effects of niacina-
cinamide-containing galenic systems [15]. There are in- mide that have to date been proven in vitro.
dications that these effects can be relevant for dermato-
logical practice (fig. 1).
by activating the mRNA expression of serine palmito-
Anti-Inflammatory Effect yltransferase, the key enzyme for the sphingolipid syn-
Niacinamide is a sufficient inhibitor of the nuclear thesis [30]. As a result the increased rate of ceramide
poly(ADP-ribose) polymerase-1 (PARP-1) that controls synthesis again influences the barrier effect of the stra-
the NFκB-mediated transcription and is therefore very tum corneum [31, 32]. Niacinamide is also a potent in-
important for the expression of adhesion molecules and hibitor of cAMP-phosphodiesterase, stabilises the mast
pro-inflammatory mediators [19–21]. Niacinamide can cells and therefore reduces the release of histamine [33–
also inhibit the expression of MHC-II as well as the pro- 39].
duction of IL-12, TNF-α, IL-1 and nitric oxide [22–24].
Niacinamide and its derivative N-methylnicotinamide Lightening Effect
increase vascular permeability by influencing the nitric Niacinamide blocks reversibly the transfer of melano-
oxide metabolism and the prostaglandin synthesis [25]. somes from melanocytes into keratinocytes by inhibiting
This perfusion-enhancing effect can be used in plastic keratinocyte factors [40–44]. This distinguishes niacina-
surgery [26, 27]. However, these anti-inflammatory ef- mide from other ‘lightening’ substances (e.g. arbutin, ko-
fects are not based on direct vasogenic effects but mainly jic acid) that inhibit tyrosinase directly [45].
on the inhibition of leucocyte chemotaxis, the release of
lysosomal enzymes, and the transformation of lympho- Antimicrobial Effect
cytes [28]. Also, regulating effects on neutrophil granulo- Preclinical data exist that demonstrate the tuberculo-
cytes have been described in the literature, although these static and antiretroviral effects of niacinamide [46–50].
are considered to have no practical relevance [29]. The effect against Mycobacterium tuberculosis can be ex-
plained with the inhibition of the class III NAD-depen-
Antipruritic Effect dent deacetylase-protein family (Sir2) [51], whereas the
The antipruritic effects of niacinamide are mainly effect against HIV is based on the inhibition of the nucle-
based on barrier-protective effects. Niacinamide is in- ar PARP [47, 52]. There are also indications that niacina-
volved in the biosynthesis of ceramides in keratinocytes mide has fungistatic effects [53].
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312 Skin Pharmacol Physiol 2014;27:311–315 Wohlrab/Kreft

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DOI: 10.1159/000359974
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 Photo-Protective Effect gel. However, a follow-up study could not prove any addi-
The photo-protective effect of niacinamide is based on tive effects for 4% niacinamide and 1% clindamycin [65].
both the inhibition of photocarcinogenesis and the protec- In a different clinical setting Draelos et al. [67] showed the
tion against UV-induced immunosuppression [54–57]. inhibiting effect of a preparation containing 2% niacina-
mide on facial sebum production. There are no clinical
data explicitly proving the postulated antipruritic effect.
Clinical Efficacy after Topical Application For the treatment of hyperpigmentation, preparations
containing up to 5% niacinamide have been used. Studies
Topical niacinamide, mostly via cosmetic prepara- with Asian subjects have shown clinically relevant effects
tions, has been widely used for quite some time now and of skin lightening after using a preparation containing 5%
is considered to be safe up to a concentration of 4% [58]. niacinamide twice daily for 8 weeks [68, 69]. Kimball et al.
However, the practical relevance of the effects described [70] could also prove lightening of facial hyperpigmenta-
here cannot explicitly be proven since there are hardly tion in a randomised, double-blinded study. No clinical
any clinical data available, and the few data that exist have data exist to prove the effect of niacinamide regarding der-
only limited relevance. Also, the data and publications matologically relevant infections. Moloney et al. [71] in-
available often do not indicate what galenic concept the vestigated the effectiveness of a 1% niacinamide prepara-
preparations were based on, or whether and in which tion versus vehicle regarding the number of actinic kerato-
quantity the cutaneous bioavailability of niacinamide in ses over 6 months and could not find relevant differences.
the target compartment has been validated. Nevertheless, In studies with recall antigen tests Gensler [72] could prove
the data provide some interesting points for the derma- in vivo that niacinamide reduces UV-induced immuno-
tologist concerning topical therapy. suppression. Further studies of photocarcinogenesis and
Study data regarding anti-inflammatory effects exist for photoprotection do not exist.
atopic dermatitis [59, 60], psoriasis [59, 61, 62], rosacea
[63, 64] and acne vulgaris [65, 66]. However, the design and
clinical end points of these studies are not appropriate to Conclusion
prove the clinical effectiveness of the respective prepara-
tions; they are pilot studies. In a study with 28 patients with In summary, it can be stated that niacinamide has suit-
atopic dermatitis Soma et al. [32] could show a reduction able physicochemical properties for topical application
in transepidermal water loss after an 8-week treatment us- and can be considered safe. The existing preclinical data
ing a preparation containing 2% niacinamide. Draelos et show that niacinamide has potential for topical applica-
al. [64] could also show barrier-protective effects in a study tion in cosmetic preparations because of its barrier-pro-
with 50 patients with rosacea. Shalita et al. [65] published tective, anti-inflammatory and depigmenting effects. The
data of a multicentre study with acne patients showing the existing clinical data suggest that the use of niacinamide
superiority regarding the effectiveness of a preparation might be worthwhile in basic therapy of atopic dermatitis
containing 4% niacinamide compared to 1% clindamycin as well as in lightening preparations.

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