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A Review of the range of effects of niacinamide in human skin

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Abstract
Niacinamide (also known as nicotinamide,
3-pyridinecarboxamide) is the physiologi-
cally active form of niacin or vitamin B3, the
deficiency of which results in the nutritional
disease pellagra with distinct cutaneous
manifestations. Since its discovery and iso-
lation, a host of dermatological therapeutic
benefits and mechanisms have also been
ascribed to this essential water-soluble vit-
amin when used as a topical agent. These in-
clude its apparent role as an anti-acne ac-
tive, an up-regulator of epidermal sphingo-
lipid synthesis, an up-regulator of markers of
epidermal differentiation and dermal prolif-
eration (with concurrent stratum corneum
barrier benefits), and as a moderator of pho-
toimmunesuppression and accompanying
tumor genesis. More recently, fresh evi-
dence points to a role in modifying the cos-
metic appearance of skin through suppres-
sion of epidermal melanosome transfer with
subsequent effect on skin pigmentation and
a role in modifying epidermal surface topo-
graphy. The mechanisms for these cutane-
ous effects are still unclear. However, since
niacinamide is an important precursor of
NADH and NADPH, it has been postulated
that topical application of niacinamide can
promote this reported broad spectrum of
activity through local correction of homeo-
static balance of these two nucleotide coen-
zymes. As there has been a dramatic in-
crease in research into and use of niacin-
amide in recent years, this review will cover
the current scope of knowledge of this im-
portant vitamin, including mechanistic un-
derstanding and cutaneous physiological
activity.
History of Niacinamide
Niacinamide is the amide of vitamin B3, also
known by the pseudonym »Vitamin PP«, that
is, »Pellagra-Preventive«. The name is not
without meaning. The first case of pellagra
was reported in the U.S. in 1902; four
decades of a pellagra epidemic followed
during which, in states south of the Potomac
and Ohio rivers, some 3 million cases and
100,000 deaths were reported [1]. Pellagra
patients presented with a variety of debili-
tating symptoms including, significantly, a
spectrum of cutaneous lesions. Tragically,
this led to the public exclusion of thousands
of victims, who came almost exclusively
from poor, rural, working-class families who
fed themselves on a bland staple diet of
cornmeal, molasses and fatback. Joseph
Goldberger, a Hungarian emigrant who es-
tablished himself as a renowned clinical epi-
demiologist, reversed steadfast medical
opinion that pellagra was an infectious,
communicable disease. He proved that sim-
ple dietary supplementation could both pre-
vent and cure pellagra. In 1927, after 13 years
of work, Goldberg persuaded the American
Red Cross to distribute dried yeast to Mis-
sissippi flood victims and, thus, prevented a
further devastating epidemic. It was not un-
til 1937 that nicotinic acid and its derivatives
(including niacinamide) were shown to be
the elusive »PP« factor. By 1945, Goldber-
ger’s legacy was permanent; public educa-
tion had changed forever the poor diet of the
South and pellagra was eliminated in the
United States.
Physiological Role of Niacinamide
The substituted pyridine derivative niacin-
amide is an essential constituent of the oxi-
doreduction coenzymes nicotinamide ade-
nine dinucleotide (NAD) and nicotinamide
adenine dinucleotide phosphate (NADP)
(Fig. 2). During glycolysis and the TCA cycle,
10 molecules of NAD+(per molecule of glu-
cose) are reduced to 10 NADH by the trans-
fer of a hydride ion to the 4-position of the
niacinamide ring. The hydride ion of NADH
serves effectively as an energy storage unit,
giving up a pair of high-energy electrons to
the mitochondrial electron transport chain
when needed. In this process of oxidative
phosphorylation, electron pairs are trans-
ferred from NADH to a final acceptor (oxy-
gen) via a series of electron carriers. This
transfer of electrons is thermodynamically
A Review of the Range of Effects of
Niacinamide in Human Skin
Paul J. Matts1), John E. Oblong2) and Donald L. Bissett2)
Keywords: Niacinamide, nicotinamide, skin, ceramide, ageing, differentiation, barrier
IFSCC Magazine – vol. 5, no 4 / 2002
1) The Procter & Gamble Company, Rusham Park Technical Centre, Egham, Surrey, UK
Email: matts.pj@pg.com
2) Miami Valley Laboratories, Cincinnati, Ohio, USA
Fig. 1: Pellagra suffer, US South, early 20th
century
The authors acknowledge the Waring Historical
Library of the Medical University of South Caroli-
na, Charleston, SC
286
favorable, i.e., G is negative, and is coupled
to the pumping of protons out of the mito-
chondrial matrix. The flow of protons back
into the matrix, in turn, catalyses the pro-
duction of ATP by F0F1ATP-synthase. Total
energy yield (G’) for this process is high
(–52.7kcal).
Whereas NADH is involved in catabolism,
NADPH tends to serve as an electron (hy-
dride ion) donor in anabolic processes, that
is, biosyntheses. For example, NADPH is the
reducing co-factor used by fatty acid syn-
thetase in lipid biosynthesis and by desmo-
lases and hydroxylases in steroid biosynthe-
sis.
Nicotinamide Coenzymes in Skin
are Depleted with age; Niacin-
amide can Help Normalize this Im-
balance
NADH and NADPH can, thus, be viewed as
fundamental energy »currency« units within
cells, driving the metabolism of cells involv-
ed in both catabolic and anabolic process-
es. There is an increasing pool of evidence
for a decline in systemic and intracellular
concentrations of these two coenzymes
with age in human and animal models [2,3,4]
and recent new data appear to confirm this.
Oblong et al. [5] established human dermal
fibroblast cell lines from a 7-year old and a
72-year old and used these to measure en-
dogenous NADPH/NADP+ratios and total
NADPH + NADP+levels. It was found that
fibroblasts from the aged donor contained
decreased NADP redox ratios and total
NADPH + NADP+levels relative to those
from the young donor (51% and 28% respec-
tively). It does appear, therefore, that there
is a reduction in nicotinamide coenzymes
associated with senescence.
Importantly, Oblong et al. [5] also found that
supplementation of human dermal fibroblast
cultures derived from elderly donors with
14C-niacinamide and 14C-nicotinic acid
(niacinamide precursor) increased intracel-
lular concentrations of NADPH. It appears
that a localized supply of niacinamide, there-
fore, can be utilized by aged cutaneous cells
to restore intracellular nicotinamide coen-
zyme homeostasis.
It is worth noting, however, that despite the
efficacy noted above, nicotinic acid (niacin)
produces a well-documented cutaneous va-
sodilatation (»flushing«) when applied to-
pically. Niacin, therefore, presents a chal-
lenge to cosmetic applications; there are no
such issues with the use of niacinamide.
Aged Fibroblasts Secrete Less
Collagen than Young Cells;
Niacinamide can Stimulate New
Collagen Synthesis
Oblong et al. [5] used 14C-proline to monitor
incorporation of label into collagen protein
secreted from cultured human dermal fibro-
blasts taken from a young (7-year old) and
aged donor (72-year old). 14C-hydroxyproline
(as a marker of newly-synthesized secreted
collagen) and 14C-proline (as a marker of to-
tal protein) were extracted, separated and
quantified using HPLC equipped with a ra-
diometric detector. Results indicated firstly
that dermal fibroblasts from an aged donor
secreted significantly (p<0.05) less collagen
than those from a young donor and, further-
more, that NADPH / NADP redox ratios were
also lower (p<0.05) in fibroblasts from the
aged donor (results were normalized to the
cell number from the respective culture
well). Secondly, it was found that supple-
mentation of the aged cell culture with
niacinamide produced significant increases
in total collagen secreted (by 54%), total pro-
tein secreted (by 41%) and also in the num-
ber of cells (by 20%), relative to a vehicle
control. Importantly, there was also a signif-
icant 35% increase in the collagen / total pro-
tein ratio (relative to a vehicle control), indi-
cating some specificity for collagen biosyn-
thesis and secretion. These data suggest,
therefore, that treatment with niacinamide
would have a positive impact on the dermal
compartment, both in terms of its connective
tissue and gel matrix components. These
effects would be of particular significance in
aged and photodamaged skin.
Niacinamide Up-regulates Epider-
mal Ceramide Synthesis with Con-
current Epidermal Barrier Benefits
Ceramides are now known to play a central
role in the structural and functional integrity
of the stratum corneum barrier function. A
decrease in ceramide fraction has been re-
ported in aged and atopic skin [6]. Tanno et
al. showed that in cultured human epidermal
keratinocytes, niacinamide could induce up
to a 5-fold up-regulation in ceramide syn-
thesis (p<0.05) in a dose-dependent fashion
[7]. Further work by the same group [8]
showed up-regulation of other sphingolipid
fractions (glucosylceramide and sphingo-
myelin) as well as free fatty acid and cho-
lesterol synthesis (by 2.3 and 1.5-fold, re-
spectively). The workers proposed a mech-
anism for these observations based on in-
creased levels of intra-cellular acetyl-CoA
(the precursor common to epidermal lipid
synthesis) and increased expression of ser-
ine-palmitoyltransferase. Tanno et al. [8] al-
so showed that these in-vitro results had
clinical significance in-vivo. Topical applica-
tion of a vehicle containing 2% niacinamide
IFSCC Magazine – vol. 5, no 4 / 2002
Fig. 2: Structure of niacinamide and inclusion within NAD molecule
287
to dry lower legs over 4 weeks induced a
measurable significant increase (p<0.05) in
recovered stratum corneum ceramide and
free fatty acid lipid fractions, vs. a vehicle
control. This was accompanied by a signifi-
cant reduction (p<0.05) in TEWL vs. vehicle
control (–27%). Similar significant reduc-
tions in TEWL vs. a vehicle control were not-
ed also by Ertel et al. [9] after use of a mois-
turizing vehicle containing 2% niacinamide.
Furthermore, they also noted that this posi-
tive barrier effect was accompanied by an
increase in stratum corneum turnover rate
(as measured by dansyl chloride assay). Fi-
nally, Draelos et al. [10] treated 48 female
subjects with stage I/II rosacea with a mois-
turizing vehicle containing 2% niacinamide
for 4 weeks and demonstrated a significant
improvement in global condition (assessed)
in 96% of the subjects at week 4. They de-
monstrated, once again, that this clinical
benefit was accompanied by a significant
improvement in stratum corneum barrier
function.
It appears that topical niacinamide is able to
augment the barrier properties of the skin,
with accompanying clinically relevant ben-
efits, by up-regulating endogenous biosyn-
thesis of epidermal sphingolipids, in partic-
ular, ceramides.
Niacinamide Up-regulates
Biosynthesis of Markers of
Keratinocyte Differentiation
Oblong et al. [5] cultured normal human epi-
dermal keratinocytes to near-confluency
and then supplemented the medium with
niacinamide. Following a 24h incubation,
cells were counted, harvested and prepared
for assay for involucrin (by ELISA) and filag-
grin (by an immunoblot procedure). Results
showed firstly a significant increase (p<0.05)
in the number of niacinamide-treated NHEK
relative to a vehicle control. Secondly, ni-
acinamide-treated NHEK showed an up-
regulation of both involucrin and filaggrin
biosynthesis vs. that induced by a vehicle
control (by 45% and 100% respectively).
These two proteins are both critical to the
differentiation process and the formation of
fully integral keratinized corneocytes; filag-
grin plays a vital role in aggregation and
alignment of keratin tonofilaments in granu-
lar cells and involucrin is an essential pre-
cursor in the formation of the insoluble
cornified envelope surrounding terminal
keratinocytes. In other words, niacinamide
has been shown to both stimulate basal epi-
dermal keratinocytes and to up-regulate
biosynthesis of epidermal intermediates
critical to the formation of a fully functioning
stratum corneum. This may be due to in-
creased intracellular levels of reduced
nicotinamide coenzymes initiated by topical
niacinamide. These effects would be ex-
pected to have a significant positive impact
on ageing epidermal tissue in-vivo.
Niacinamide Helps Prevent
UV-Induced Deleterious Molecu-
lar and Immunological Events
Shen et al. [11] demonstrated the ability of
niacinamide to protect cultured normal hu-
man keratinocytes against reactive oxygen
species induced by UVC irradiation or expo-
sure to hydrogen peroxide. They observed
significant (p<0.05) dose-dependent attenu-
ation of apoptotic morphological changes, a
decrease in p53 induction and a reduction in
DNA ladders for niacinamide-treated cells
vs. those treated with a vehicle control.
These data are consistent with work in ani-
mal models [12] demonstrating clearly the
ability of niacinamide to significantly reduce
both induction of photocarcinogenesis and
photoimmunesuppression. The mechanism
by which niacinamide exerts these effects is
not yet clear.
Niacinamide Inhibits Transfer of
Melanosomes from Melanocytes
to Keratinocytes
Boissy et al. [13] used co-cultures of human
melanocytes and keratinocytes to investi-
gate the ability of niacinamide to reduce pig-
mentation in human skin. Use of immuno-
linked dyes specific for each cell type en-
abled separate counts of keratinocytes,
melanocytes and keratinocytes containing
transferred melanosomes to be performed.
The workers found significant inhibition
(p<0.05) of melanosome transfer to keratino-
cytes from melanocytes incubated in the
presence of niacinamide (by 25-45%). It was
also confirmed that niacinamide had no in-
hibitory effect on melanocyte tyrosinase
activity. These data suggest that treatment
of human skin in-vivo with topical niacin-
amide would lead to a reduction in pigmen-
tation with time via this novel, elegant mech-
anism.
Niacinamide Reduces Human
Skin Hyperpigmentation
Hakozaki et al. [14] performed two studies
demonstrating the effect of niacinamide on
skin hyperpigmentation in-vivo. In the first,
18 female Japanese subjects with hyperpig-
mented facial spots were treated for 8
weeks with a vehicle containing 5% niacin-
amide vs. a vehicle control in a split-face de-
sign. Pigmented spots were qualified and
quantified via algorithmic analysis of high-
resolution digital images and subjective
grading of images. Results of image analysis
showed that 5% niacinamide had induced a
significant (p<0.05) reduction in spot area at
the 4 and 8 week time-points (vs. vehicle
control), accompanied by a significant re-
duction (p<0.05) in graded visible spot pig-
mentation at 8 weeks (vs. vehicle control). In
the second study, 120 female Japanese sub-
jects with facial tanning were assigned to 2
of 3 treatments (SPF 15 sunscreen moistur-
izer, 2% niacinamide in SPF 15 sunscreen
moisturizer and a vehicle control). Subjects
applied treatments split-face for 8 weeks. In
this study overall skin lightness was as-
sessed by analysis of digital images and by
subjective grading. Results of image analy-
sis showed a significant (p<0.05) increase in
skin lightness vs. the sunscreen moisturizer
and vehicle control at the 4 and 6 week time-
points, accompanied by a significant
(p<0.05) increase in graded visible skin light-
ness vs. vehicle control at 4 weeks. These
in-vivo data appear to confirm, therefore,
that the inhibitory role of niacinamide in
melanosome transfer noted in-vitro [13],
does indeed translate to a significant effect
on hyperpigmentation in-vivo.
Regulation of Sebaceous Lipid and
Acne by Niacinamide
Topical niacinamide in the form of a com-
mercial 4% gel (Papulex®) has been shown
to provide potent anti-inflammatory activity
in the treatment of acne vulgaris. Shalita et
al. [15] found that after 8 weeks of usage,
82% of subjects with inflammatory acne
showed an improvement in global evalua-
tion, with a significant reduction in papules /
pustules (–60%) and acne severity (–52%).
Indeed, many practitioners use the treat-
ment citing a combination of efficacy and
lack of bacterial-resistance. Shalita et al.
[15] and others postulate that niacinamide
IFSCC Magazine – vol. 5, no 4 / 2002
288
may act via its apparent antihistaminic ef-
fect, activity as an electron scavenger, or its
inhibition of 3’-5’ cyclic-AMP phosphodi-
esterase activity.
Recent data, however, appear to demon-
strate an altogether more fundamental role
for topical niacinamide in acne treatment.
Biedermann et al. [16] used viable human fa-
cial biopsies (from face-lift surgery) to mea-
sure the effect of niacinamide on sebaceous
lipogenesis. Cultured biopsies were treated
with niacinamide or trans-retinoic acid (tRA)
for 4 days, after which they were incubated
with 14C-acetate. Lipid components were
subsequently isolated, fractionated and
identified using analytical TLC and radiome-
try. Niacinamide produced significant dose-
dependent reductions in total sebaceous
lipogenesis (–42% at 25 mM [p<0.01]). Fur-
thermore, the reduction induced by 25 mM
niacinamide was equivalent to that pro-
duced by 1 µM tRA (–32% [p=0.01]). When
discrete lipid classes were identified and
quantified, it was found that niacinamide
had produced marked reductions in both
triglyceride and fatty acid synthesis vs. the
control (–52% and –46% respectively for 25
mM niacinamide [p<0.05]). It is now known
that triglycerides represent by far the largest
proportion of sebaceous gland lipid (50-
60%); the observed effect of niacinamide on
total lipogenesis is, therefore, probably at-
tributable to triglyceride reduction.
This has important implications for acne
pathogenesis. It is accepted that acne is a
disease involving the pilosebaceous duct
and Propionibacterium acnes. Despite the
on-going debate as to the exact interplay of
these factors, it is without doubt that a sig-
nificant reduction both in total sebaceous
lipid bulk and in the triglyceride fraction
would be expected to impact positively
acne-form skin.
Niacinamide Exerts Multiple
Benefits on the Appearance of
Ageing / Photodamaged Skin,
In-vivo
Bissett et al. [17] studied the effects of topi-
cal niacinamide in ageing human facial skin
in two double-blinded clinical studies. In the
first, 40 female subjects aged 35 - 60 applied
a vehicle and vehicle containing 5% niacin-
amide (randomized split-face) for 12 weeks.
High-resolution digital images were taken at
baseline, 4, 8 and 12 weeks and texture and
hyperpigmentation were evaluated by
judges (comparing blind-coded image pairs,
baseline vs. another treatment time-point).
Judges were able to perceive a significant
improvement in skin texture appearance at
4 weeks (p<0.1) and 12 weeks (p<0.05) and a
significant improvement in hyperpigmented
spot appearance by 8 weeks (p<0.05) (Fig. 3).
In a second study, female subjects aged 35-
60 applied blind-coded products (vehicle
control and vehicle containing 5% niacin-
amide; n=88) split-face for 8 weeks. Skin tex-
ture appearance was assessed as above.
The niacinamide-containing treatment pro-
vided a significant improvement in skin tex-
ture appearance relative to the vehicle con-
trol at the 8 week time-point, confirming the
results of the first study.
This effect on skin surface texture is consis-
tent with that noted in a 10-week clinical
study where Matts & Solechnick [18] used
multiple-angle reflectance spectrophoto-
metry to measure the diffuse component of
skin reflection. They noted a significant in-
crease in the diffuse component of 5%
niacinamide-treated dorsal hand skin vs.
vehicle control after 10 weeks of treatment
(p<0.05), consistent with significant blind
self-rated preferences for texture appear-
ance over vehicle control (p<0.05). This
change was consistent with a shift in texture
distribution towards the finer, anisotropic
features characteristic of younger skin.
Niacinamide is Delivered Effec-
tively from a Range of Vehicles
and Demonstrates Excellent Skin
Compatibility
Franz [19] determined niacinamide absorp-
tion in-vitro through full-thickness abdomi-
nal skin mounted in flow-through diffusion
cells. Franz used acetone as a carrier and
found 28.8% of the starting dose in the re-
ceptor medium at 24 h. Delivery of niacin-
amide (2-20%) from a range of cosmetic for-
mulae (including moisturizers, foundations
and lipsticks) was studied using a modified
in-vitro Franz flow-through cell technique
[20]. For formulae containing 2% niacin-
amide, approximately 10% of the starting
dose was detected in the receptor medium
at 48 h. Importantly, these studies highlight-
ed the apparent independence of niacin-
amide penetration rate from diverse vehicle
matrices.
The Cosmetic Ingredient Review Expert Pan-
el report for niacinamide [21] details a very
wide range of cutaneous tolerance studies
confirming the excellent profile of niacin-
amide as a cosmetic skin care ingredient.
Conclusion
Niacinamide, therefore, has been shown to
be a cosmetic ingredient with an extraordi-
IFSCC Magazine – vol. 5, no 4 / 2002
Baseline 12 Weeks
Fig. 3: Same subject at baseline and after 12 weeks of topical treatment with 5% niacinamide
289
nary breadth and history of cutaneous ben-
efits. It is thought that its fundamental role as
a precursor of reduced nicotinamide coen-
zymes such as NADH and NADPH is pivotal
to its observed effects. It displays distinct
advantages over other ingredients with sim-
ilar benefits, such as retinol, in that it is well
tolerated, and is not subject to oxidation or
photolysis. In short, the multiplicity of effects
and formulation benefits seen with niacin-
amide make it an ideal choice for a variety of
cosmetic products targeting young and old
skin alike.
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IFSCC Magazine – vol. 5, no 4 / 2002
... A niacinamida (NIA), vitamina hidrossolúvel que integra a família B3, é um componente encontrado em nucleotídeos de piridina, a nicotinamida adenina dinucleotídeo (NAD) e a nicotinamida adenina dinucleotídeo fosfato (NADP), as quais, são coenzimas envolvidas fisiologicamente na transferência de hidrogênio e reações de oxirredução, responsáveis por transformar nutrientes em energia. A niacinamida também atua no aumento da síntese de queratina e diferenciação de queratinócitos (Matts;Bissett, 2002;Gehring, 2004). ...
... A niacinamida (NIA), vitamina hidrossolúvel que integra a família B3, é um componente encontrado em nucleotídeos de piridina, a nicotinamida adenina dinucleotídeo (NAD) e a nicotinamida adenina dinucleotídeo fosfato (NADP), as quais, são coenzimas envolvidas fisiologicamente na transferência de hidrogênio e reações de oxirredução, responsáveis por transformar nutrientes em energia. A niacinamida também atua no aumento da síntese de queratina e diferenciação de queratinócitos (Matts;Bissett, 2002;Gehring, 2004). ...
... Eles podem ser de caráter farmacológico e não farmacológico. Os tratamentos não farmacológicos incluem terapias a laser, que utilizam feixes de luz concentrada para tratar problemas como manchas escuras, cicatrizes de acne, rugas e vasos sanguíneos dilatados (Matts;Bissett, 2002). Dentre as opções disponíveis de tratamento farmacológico, destacam-se os medicamentos tópicos sendo utilizados no tratamento de condições como acne, eczema, psoríase e dermatite de contato (Araujo et al., 2021). ...
Article
A niacinamida é uma vitamina hidrossolúvel que tem sido amplamente estudada por suas propriedades antioxidantes, anti-inflamatórias e regenerativas, que podem contribuir para a saúde cutânea quando utilizada dermatologicamente. Contudo, é necessário que a concentração do ativo e a classificação do produto sejam adequadas para o fim desejado. Dessa maneira, o presente estudo objetivou comparar a composição química dos cosméticos registrados na Anvisa de maneira a avaliar o seu perfil químico e sua segurança. Para isso foi realizada uma pesquisa descritiva quantitativa no site da Anvisa dos produtos registrados que continham niacinamida e comparou-se sua formulação. Os resultados mostraram que a maioria dos produtos (40,6%) são séruns, seguidos por hidratantes faciais (12,3%); apenas 32,1% dos produtos possuem comprovação científica de sua eficácia; os produtos classificados como grau 2 apresentaram maior concentração de niacinamida do que os produtos grau 1. Logo, foi possível considerar que os produtos cosméticos contendo niacinamida são seguros e eficazes, entretanto é importante verificar a concentração do ativo bem como dos demais componentes e buscar a orientação de um profissional capacitado antes do uso.
... It inhibits melanosome transfer to keratinocytes, which helps brighten the skin and further evens out the skin tone. 15 Moreover, it stimulates the synthesis of basal keratinocyte and other intermediates, essential for the formation of a healthy stratum corneum. 15 Sea daffodils were also rated as excellent by most HCPs for reducing dark spots and hyperpigmentation in the current survey. ...
... 15 Moreover, it stimulates the synthesis of basal keratinocyte and other intermediates, essential for the formation of a healthy stratum corneum. 15 Sea daffodils were also rated as excellent by most HCPs for reducing dark spots and hyperpigmentation in the current survey. A study examining the efficacy of sea daffodils for pigmented spots revealed that these inhibit melanin synthesis by acting on the substance P receptor present on melanocyte dendrites. ...
Article
Full-text available
Background: Niacinamide has demonstrated its ability to treat dark spots in various studies. The present study evaluated the perspectives and experiences of healthcare professionals (HCPs) and patients with the niacinamide and sea daffodils-based bright healthy radiance product range for dark spots. Methods: This study was part of a survey series focusing on various dermatology products across India. The study involved over 1000 registered HCPs including dermatologists, pediatricians, and cosmetologists nationwide. A total of 203 HCPs participated in the survey on the niacinamide and sea daffodils-based product range. A well-structured questionnaire with 15 questions was used to collect the data and the responses were recorded by the HCPs. Results: Out of the total of 1086 individuals who participated in the survey, majority were females (774, 71.2%). Most HCPs reported that nearly 15-30% of their patients present with dark spots. A vast majority of individuals reported extreme satisfaction with the use of niacinamide and sea daffodils-based bright healthy radiance product range (493, 45.5%) and rated its effectiveness as excellent (511, 47.2%). HCPs reported that most patients showed major improvement in skin brightness (529, 48.7%), while the rest of them (418, 38.4%; 137, 12.6%) experienced good and satisfactory improvement respectively. Importantly, an even skin tone was achieved in most of the patients (492, 45.8%) after the application of the product range. Conclusions: A personalized approach of using niacinamide and sea daffodil-based products according to the patient's skin types and skin conditions is essential to remove blemishes and dark spots and improve skin brightness.
... Niacinamide (nicotinamide) is the heterocyclic aromatic amide form of water-soluble vitamin B3 (niacin). Vitamin B3 deficiency can lead to a disease known as Pellagra [1]. Niacinamide has been used for anti-hyperpigmentation/anti-aging applications [2,3], as an anti-oxidant [4], improving skin barrier function [5], and for alleviating some skin conditions such as acne vulgaris [6] and dermatitis [7]. ...
Article
Full-text available
Niacinamide, a derivative of vitamin B3, has been shown to reduce skin pigmentation (i.e., acting as a brightening agent) and inflammatory responses such as dermatitis and acne vulgaris. However, niacinamide is a hydrophilic compound and poor partitioning to the lipid matrix in the uppermost layer of the skin (the stratum corneum or SC) limits its delivery to the skin. This necessitates the use of penetration enhancers to increase its bio-availability. In this study, we used computer simulations to investigate the skin penetration of niacinamide alone and in combination with other brightening agents that are also shown to be skin penetration enhancers, namely undecylenoyl phenylalanine (Sepiwhite®), bisabolol, or sucrose dilaurate. Molecular dynamics simulations were performed to reveal molecular interactions of these brightening agents with a lipid bilayer model that mimics the SC lipid matrix. We observed minimal penetration of niacinamide into the SC lipid bilayer when applied alone or in combination with any one of the three compounds. However, when all three compounds were combined, a notable increase in penetration was observed. We showed a 32% increase in the niacinamide diffusivity in the presence of three other brightening agents, which also work as penetration enhancers for niacinamide. These findings suggest that formulations containing multiple brightening agents, which work as penetration enhancers, may improve skin penetration of niacinamide and enhance the effectiveness of the treatment.
... Cosmeceuticals often contain biologically active compounds such as antioxidants, peptides, vitamins, and growth factors designed to provide benefits beyond basic skincare. Many cosmeceuticals focus on anti-aging effects, aiming to reduce the appearance of fine lines, wrinkles, and other signs of skin aging [7]. Some cosmeceuticals include ingredients that promote the synthesis of collagen and elastin, crucial proteins for skin elasticity and firmness [8,9]. ...
... Niacin, a precursor to the enzyme cofactors nitinamide adenine dinucleotide (NAD), phosphorylated derivative (NADP), and reduced forms (NADH, NADPH), plays crucial roles in cell metabolism and regeneration. The numerous cosmetic benefits associated with the topical application of niacinamide can be attributed to the intricate processes associated with these cofactors (Matts et al., 2002). Increased barrier function in both normal participants and acne patients with sensitive skin has been linked to improvements in the appearance of skin following topical niacinamide application (DL, 2003;Draelos et al., 2005). ...
Chapter
This chapter explores the challenges and opportunities in cosmeceutical formulations incorporating natural excipients. Researchers face stability and formulation issues due to the use of botanical, mineral, and biocompatible materials. To maintain potency, innovative biotechnology and green chemistry solutions have been developed. Nanoencapsulation methods improve the stability and bioavailability of natural actives. Synergistic combinations of bioactive ingredients and botanical extracts offer new treatments for various skin conditions. Natural cosmeceuticals are a combination of scientific research and botanical knowledge aimed at sustainable skincare products. A nuanced understanding of these opportunities and challenges is crucial for a sustainable future for environmental stewardship and skincare innovation.
... It is the amide form of niacin, which can also be endogenously synthesized in the liver from the essential amino acid tryptophan. Niacinamide is currently used extensively in cosmetic products due to its ample beneficial applications for skin health, including skin barrier and elasticity improvement, increased collagen and epidermal ceramide synthesis, reducing skin diseases such as hyperpigmentation, rosacea and acne, and improving overall skin appearance [1][2][3][4][5][6][7][8][9]. ...
Article
Full-text available
Niacinamide is a versatile compound widely used in the personal care industry for its ample skin benefits. As a precursor to nicotinamide adenine dinucleotide (NAD+), essential for ATP production and a substrate for poly-ADP-ribose polymerase-1 (PARP-1), studies have highlighted its roles in DNA repair, cellular stress mechanisms, and anti-aging benefits. Niacinamide was also studied for its antimicrobial activity, particularly in the context of host-infection via host immune response, yet its direct antimicrobial activity and the mechanisms of action remain unclear. Its multifunctionality makes it an appealing bioactive molecule for skincare products as well as a potential preservative solution. This study explores niacinamide’s antimicrobial mode of action against four common cosmetic pathogens. Our findings indicate that niacinamide is causing microbial cell cycle arrest; while cells were found to increase their volume and length under treatment to prepare for cell division, complete separation into two daughter cells was prevented. Fluorescence microscopy revealed expanded chromatin, alongside a decreased RNA expression of the DNA-binding protein gene, dps. Finally, niacinamide was found to directly interact with DNA, hindering successful amplification. These unprecedented findings allowed us to add a newly rationalized preservative facete to the wide range of niacinamide multi-functionality.
... As a result, the effects of nicotinamide on the skin are well known. For example, it has been reported that nicotinamide acts in the process where aged fibroblasts secrete less collagen compared to younger cells [54]. Similarly to our research, Bissett et al. applied nicotinamide as a topical treatment in a clinical study and demonstrated its anti-aging and anti-wrinkle effects on human facial skin [55]. ...
Article
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Freesia refracta (FR), a perennial flower of the Iris family (Iridaceae), is widely used in cosmetics despite limited scientific evidence of its skin benefits and chemical composition, particularly of FR callus extract (FCE). This study identified biologically active compounds in FCE and assessed their skin benefits, focusing on anti-aging. FR calli were cultured, extracted with water at 40 °C, and analyzed using Centrifugal Partition Chromatography (CPC), Nuclear Magnetic Resonance (NMR), and HCA, revealing key compounds, namely nicotinamide and pyroglutamic acid. FCE significantly increased collagen I production by 52% in normal and aged fibroblasts and enhanced fibroblast–collagen interaction by 37%. An in vivo study of 43 female volunteers demonstrated an 11.1% reduction in skin roughness and a 2.3-fold increase in collagen density after 28 days of cream application containing 3% FCE. Additionally, the preservation tests of cosmetics containing FCE confirmed their stability over 12 weeks. These results suggest that FCE offers substantial anti-aging benefits by enhancing collagen production and fibroblast–collagen interactions. These findings highlighted the potential of FCE in cosmetic applications, providing significant improvements in skin smoothness and overall appearance. This study fills a gap in the scientific literature regarding the skin benefits and chemical composition of FR callus extract, supporting its use in the development of effective cosmeceuticals.
... Vitamins, such as vitamin E and vitamin C, contribute to the overall nourishment and protection of the lip tissue, promoting a healthier and more vibrant appearance. [12][13][14] Furthermore, the incorporation of natural ingredients like honey, beeswax, and plant-based oils, such as argan oil and rosehip oil, can provide additional moisturizing and nourishing benefits, while also contributing to the overall sensory experience of using the lip balm. ...
Article
Full-text available
Lip care cosmetics have gained immense popularity due to their ability to enhance the appearance and health of the lips. These products encompass lip balms for moisturizing and protecting, lip glosses for imparting shine and subtle color, and lip rouges (lipsticks) for bold, pigmented hues. Lip balms typically contain waxes, oils, butters, and emollients to nourish and shield lips from environmental stressors. Recent advancements involve incorporating herbal extracts, vitamins, and antioxidants for additional benefits. Lip glosses consist of oils, waxes, pigments, and additives, designed to provide a glossy finish and varying degrees of color intensity, from sheer to opaque. Their moisturizing properties, ease of application, and potential for stickiness or transfer are discussed. Lip rouges, available in solid, liquid, or glossy formulations, add vibrant color and definition to the lips. Their formulations include waxes, oils, pigments, and other additives tailored for desired textures and finishes. The historical significance of lip coloring and the growing demand for natural and herbal lip rouges are explored. Recent advances encompass long-wearing formulations, incorporation of active ingredients (anti-aging, skin-lightening), and sustainable, eco-friendly ingredients. Safety assessments and regulatory considerations are crucial for ensuring the responsible development of lip care cosmetics. Continued research and innovation are vital to meet evolving consumer needs and preferences while prioritizing safety and efficacy
Chapter
The increasing demand for youthful, radiant skin has driven the skincare industry to innovate, particularly through the development of natural cosmeceuticals. This chapter explains the efficacy of these products, focusing on their capacity to reduce skin wrinkles—a primary sign of aging. The authors examine clinical trials and case studies to understand the cellular and molecular mechanisms by which natural ingredients contribute to skin health and their anti-wrinkle effects. Additionally, the authors address challenges related to the stability and compatibility of natural ingredients in formulations, alongside their alignment with consumer preferences and market trends. The chapter concludes by assessing the potential benefits of natural cosmeceuticals in antiaging treatments and identifying key areas for future research. The goal of the presented chapter is to advance skincare science by pragmatically leveraging antiaging research to enhance product development.
Article
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The use of in vitro preparations of human skin to study percutaneous absorption is widespread. Yet, up to the present time, little has been done to systematically validate this model and demonstrate the extent to which it mimicks in vivo absorption. In this study, the permeability of 12 organic compounds has been evaluated in excised skin and the results compared to those obtained previously by others in living man. With special emphasis being given here to duplicating in vivo conditions, it was possible to demonstrate an excellent qualitative agreement between the two methods. In all cases, the absorption pattern determined in vitro rather precisely paralleled the pattern which was obtained in vivo. Quantitative agreement between the two sets of data was less than perfect, although the in vitro method adequately distinguished compounds of low permeability from those of high permeability and ranked then in approximately the same order found in vivo. This systematic comparison of in vitro with in vivo data was clearly shown how accurately in vitro absorption studies can reflect the living state.
Article
It is now well established that ageing occurs at the level of individual cells in the skin and other organ systems. Changes in cell behaviour, protein production and gene expression in response to standardized stimuli are readily observed in cultured cells derived from young vs old donors and from photoaged vs sun-protected body sites. Whether these changes are best viewed as a cause or a consequence of ageing cannot be determined at present. Nevertheless, available data now provide cellular and molecular correlates for the well-known differences in clinical responsiveness between newborn, adult and photoaged skin. From this basis, it will hopefully be possible to develop a more comprehensive understanding of cutaneous ageing processes.
Article
It has been reported that aging strikingly decreases in vivo ethanol metabolism in F344 rats without major effects on hepatic alcohol dehydrogenase (ADH) activity. Because hepatic ADH activity is not always rate limiting in the oxidation of ethanol, we measured in vivo ethanol elimination rate (EER), hepatic ADH activity, and the hepatic-cytoplasmic and mitochondrial redox states after acute ethanol application in 2- and 12-month-old F344 rats of both sexes. In male, but not in female, animals EER decreased with age significantly, by 28% (P less than 0.01). The body-to-liver weight ratio was significantly increased in male (39.4 +/- 1.5 vs 46.5 +/- 2.0; P less than 0.05), but not in female, animals with age. Specific activity of ADH was not significantly changed by age, while the activity was significantly reduced with age in male, but not female, rats when related to body weight (5.1 +/- 0.4 vs 3.9 +/- 0.3 mumoles/100 g b.wt./min; P less than 0.05). The cytoplasmic, but not the mitochondrial (NAD+) to (NADH), ratio was significantly decreased with age in male livers (317 +/- 48 vs 793 +/- 128, P less than 0.05), while this was not the case in female livers. In summary, the data show a sex dependence of the effect of age on ethanol metabolism. The observed reduction in in vivo EER with age in male animals is due at least in part to an increased body-to-liver weight ratio, decreased hepatic ADH activity, and reduced availability of NAD+, the cofactor of the ADH reaction. The cause of this may be decreased transport of reducing equivalents through the mitochondrial membrane due to a lack of shuttle systems or a change in the physicochemical properties of the mitochondrial membrane, or decreased reutilization of NADH as NADPH resulting from a reduction of microsomal ethanol oxidation with age.
Article
Stratum corneum lipids are an important determinant for both water-retention function and permeability-barrier function in the stratum corneum. However, their major constituent, ceramides, have not been analyzed in detail in skin diseases such as atopic dermatitis that show defective water-retention and permeability-barrier function. In an attempt to assess the quantity of ceramides per unit mass of the stratum corneum in atopic dermatitis, stratum corneum sheet was removed from the forearm skin by stripping with cyanoacrylate resin and placed in hexane/ethanol extraction to yield stratum corneum lipids. The stratum corneum was dispersed by solubilization of cyanoacrylate resin with dimethylformamide, and after membrane filtration, the weight of the stratum corneum mass was measured. The ceramides were quantified by thin-layer chromatography and evaluated as microgram/mg stratum corneum. In the forearm skin of healthy individuals (n = 65), the total ceramide content significantly declined with increasing age. In atopic dermatitis (n = 32-35), there was a marked reduction in the amount of ceramides in the lesional forearm skin compared with those of healthy individuals of the same age. Interestingly, the non-lesional skin also exhibited a similar and significant decrease of ceramides. Among six ceramide fractions, ceramide 1 was most significantly reduced in both lesional and non-lesional skin. These findings suggest that an insufficiency of ceramides in the stratum corneum is an etiologic factor in atopic dry skin.
Article
In cultured human skin fibroblasts the glucose flux through the hexose monophosphate shunt (HMS) amounts to 4% of the glucose flux through the glycolytic pathway. Upon in vitro ageing the rate of glucose utilization through the HMS is decreased more than 50%. This decrease in HMS was not caused by a limiting enzymatic capacity since glucose utilization through the HMS could be raised at least 30-fold in both 'young' and 'aged' fibroblasts upon stimulation with phenazine methosulphate. This effect of in vitro ageing upon glucose metabolism was also not due to differences in proliferation rate between 'young' and 'aged' human fibroblasts, since there was no difference in glucose utilization between proliferating and growth-inhibited (confluently cultured) fibroblasts. The NADPH/NADP ratio was found to be decreased by 12% in 'aged' cells.
Article
Systemic and topical antimicrobials are effective in the treatment of inflammatory acne vulgaris; however, widespread use of these agents is becoming increasingly associated with the emergence of resistant pathogens raising concerns about microorganism resistance and highlighting the need for alternative nonantimicrobial agents for the treatment of acne. Nicotinamide gel provides potent antiinflammatory activity without the risk of inducing bacterial resistance. In our double-blind investigation, the safety and efficacy of topically applied 4% nicotinamide gel was compared to 1% clindamycin gel for the treatment of moderate inflammatory acne vulgaris. Seventy-six patients were randomly assigned to apply either 4% nicotinamide gel (n = 38) or 1% clindamycin gel (n = 38) twice daily for 8 weeks. Efficacy was evaluated at 4 and 8 weeks using a Physician's Global Evaluation, Acne Lesion Counts, and an Acne Severity Rating. After 8 weeks, both treatments produced comparable (P = 0.19) beneficial results in the Physician's Global Evaluation of Inflammatory Acne; 82% of the patients treated with nicotinamide gel and 68% treated with clindamycin gel were improved. Both treatments produced statistically similar reductions in acne lesions (papules/pustules; -60%, nicotinamide vs. -43%, clindamycin, P = 0.168), and acne severity (-52% nicotinamide group vs. -38% clindamycin group, P = 0.161). These data demonstrate that 4% nicotinamide gel is of comparable efficacy to 1% clindamycin gel in the treatment of acne vulgaris. Because topical clindamycin, like other antimicrobials, is associated with emergence of resistant microorganisms, nicotinamide gel is a desirable alternative treatment for acne vulgaris.
Article
Ultraviolet (UV) B irradiation leads to a potent immunosuppression of the capacity to reject syngeneic, antigenic tumors. If this immunosuppression is critical for the development of most skin tumors, then its prevention should result in prevention of photocarcinogenesis. We previously showed a correlation between the inhibition of photoimmunosuppression and prevention of photocarcinogenesis by dl-alpha-tocopherol, tannic acid, or alpha-difluoromethylornithine. The current study was designed to determine whether topical nicotinamide, the active form of vitamin B-3, or niacin, prevents immunosuppression and skin cancer in UV-irradiated mice. In a passive transfer assay for immunosuppression, splenocytes from UV-irradiated mice enhanced the growth of antigenic tumor challenges in recipient mice. Treatment of the UV-irradiated mice with 40 mumol of nicotinamide twice weekly starting two weeks before UV irradiation and throughout the experiment prevented this immunosuppression. UVB irradiation consisted of five weekly 30-minute exposures to banks of six FS40 Westinghouse fluorescent sunlamps. Mice received approximately 6.2 x 10(5) J/m2 in the passive transfer assays and 1.09 x 10(6) J/m2 in the photocarcinogenesis studies. Application of nicotinamide to UV-irradiated mice reduced skin tumor incidence from 75% to 42.5% (p = 0.016, Cox proportional hazards analysis). Thus topical nicotinamide prevented the immunosuppression and skin tumor induction by UVB irradiation.
Article
Pellagra was in existence for nearly two centuries in Europe before being recognized in the United States, where it was first reported in 1902. Over the next two decades, pellagra occurred in epidemic proportions in the American South. Poverty and consumption of corn were the most frequently observed risk factors. Since the exact cause and cure of pellagra was not known, a culture of "pellagraphobia" formed among the public. Patients were shunned and ostracized. The medical community implicated spoiled corn as the cause of pellagra, which had economic repercussions for agriculturists. Joseph Goldberger, MD, of the United States Public Health Service eventually solved the secret of the malady: faulty diet. Goldberger was able to prevent and induce pellagra by dietary modification, a landmark event in the annals of medicine, nutrition, and epidemiology. His work and the social history of that period are reviewed.
Article
Stratum corneum lipids, particularly ceramides, are important components of the epidermal permeability barrier that are decreased in atopic dermatitis and aged skin. We investigated the effects of nicotinamide, one of the B vitamins, on biosynthesis of sphingolipids, including ceramides and other stratum corneum lipids, in cultured normal human keratinocytes, and on the epidermal permeability barrier in vivo. The rate of sphingolipid biosynthesis was measured by the incorporation of [14C]-serine into sphingolipids. When the cells were incubated with 1-30 micromol L-1 nicotinamide for 6 days, the rate of ceramide biosynthesis was increased dose-dependently by 4.1-5. 5-fold on the sixth day compared with control. Nicotinamide also increased the synthesis of glucosylceramide (7.4-fold) and sphingomyelin (3.1-fold) in the same concentration range effective for ceramide synthesis. Furthermore, the activity of serine palmitoyltransferase (SPT), the rate-limiting enzyme in sphingolipid synthesis, was increased in nicotinamide-treated cells. Nicotinamide increased the levels of human LCB1 and LCB2 mRNA, both of which encode subunits of SPT. This suggested that the increase in SPT activity was due to an increase in SPT mRNA. Nicotinamide increased not only ceramide synthesis but also free fatty acid (2.3-fold) and cholesterol synthesis (1.5-fold). Topical application of nicotinamide increased ceramide and free fatty acid levels in the stratum corneum, and decreased transepidermal water loss in dry skin. Nicotinamide improved the permeability barrier by stimulating de novo synthesis of ceramides, with upregulation of SPT and other intercellular lipids.