ENHANCING SKIN TONE
RESEARCH UPDATE
DEFINING ISSUES
Changing the Tone of Skin Science
In the age-old quest to retain youthful beauty, reducing
wrinkles and fine lines has often overshadowed
maintaining even-toned skin. But a glance at art across
cultures and centuries shows that luminous, even skin
tone is considered ideal. From the palest white powders
used by Japanese courtesans to the bronzers applied by
women of today looking for even, sun-kissed color
without the risk of tanning � changing skin tone to
enhance beauty has been an ongoing interest of women
for hundreds of years. In recent years, medical science
has offered pharmacological tools to help with
pigmentation changes due to natural aging,
photodamage or skin conditions, and many of these
tools and understandings are now being reapplied to the
world of cosmetics. Still, the connection between skin
tone, skin health and perception of age is only beginninge to be illuminated.
New psycho-social research is demonstrating how vital
skin tone is to age and beauty perceptions, and scientists
are gaining new insights into why skin’s luminosity and
uniformity of tone tends to degenerate with age. Using
sophisticated medical imaging tools and computational
models, scientists can now look beneath the surface of
the skin and precisely characterize age-related changes
in sub-surface structure, pigmentation and texture.
As a result of these new understandings and better
research about the underlying biology of pigment
changes, the tone of skin science is changing. Scientists
and dermatologists are beginning to recognize that
repairing tone problems is as important as repairing
texture problems, and are increasingly able to offer
women better and more accessible solutions to achieve
luminous and more even skin tone.
Advances in Science
Defining Tone
The wide range of skin colors – from the deepest
chocolate brown of Africa’s Ivory Coast to the warm
olives of the Mediterranean to the pale fairness of
Scandinavia – is paralleled by a similarly wide array of
cultural beliefs that define “ideal skin tone” in various
geographic regions. Western women may desire the
healthy glow of sun-kissed skin, while Asian cultures
value paleness, sometimes going to great lengths to
lighten skin.
Despite these seemingly contradictory goals, there is one
common quality that seems to define beautiful, desirable
skin the world over: evenness. Regardless of where on the
color spectrum any one individual is, uniform, even-toned
skin has a luminous “lit from within” quality that is
emerging as one of the most critical characteristics of
healthy, youthful attractiveness. Skin texture is also an
important piece of the tone puzzle, because smooth,
fine-textured skin reflects light more evenly.
In the case of both color and texture, contrast seems
to be the key – or more precisely, the lack of contrast.
That’s because the human eye is drawn to edges created
by contrast. Skin aging affects texture and pigmentation,
creating contrasts on the face that may be a result of
shadows caused by wrinkles or color changes caused by
age spots.
Skin tone, then, can be defined as an interplay between
even color and fine texture, both of which act to reduce
contrast and increase luminosity.
Shedding Light on “Skin Optics”
It is said that beauty is in the eye of the beholder and
scientific research has shed new light on precisely how the
human eye processes “beauty” and the roles played by
skin tone and evenness. A rich history of research
on “skin optics” has examined how the reflection and
refraction of light beneath the skin’s surface contributes
to its outward appearance.
Human skin is not a solid, opaque surface. Rather, skin
has depth and layers, and its appearance is determined by
how much light is ultimately reflected back to the eyes.
The amount and color of reflected light is, in turn,
determined by the quality and distribution of lightabsorbing
molecules (chromophores) beneath the stratum
corneum – particularly melanin, hemoglobin and collagen.
(See diagram on opposite page.)
Facial skin normally allows more than 90 percent of light
to penetrate its surface.1-5 White light passing through
skin’s transparent surface is scattered back toward the
surface by dermal collagen, which acts essentially as a
mirror within the skin. The color of this light is modified
by the chromophores, melanin and hemoglobin, both
during its journey into the skin and as it is reflected back
toward the surface. Colored light is then diffused softly at
the surface by the stratum corneum, generating a
luminous glow.
If, however, the delicate, even balance of chromophore
distribution within the skin is disrupted – as can happen
in photoaging or exposure to environmental irritants –
shadowing caused by texture, along with local changes
in pigment concentrations, can dull skin’s luminosity by
creating contrast.
Biological Facts
What Lies Beneath:
The Biology of Tone
The incredible kaleidoscope of human skin color is due to
each individual’s unique dermal concentration and
distribution of skin chromophores, molecules that absorb
or reflect light. While a number of chromophores are
present in human skin, various models of skin optics1-5
indicate that three such molecules – melanin, hemoglobin
and collagen – overwhelmingly drive skin coloration
differences both between different people and within
the same individual.
Melanin is expressed in discrete organelles (melanosomes)
that are assembled within epidermal melanocytes and are
transported, when mature, to neighboring keratinocytes.
Melanin is perceived as a brown-colored pigment,
responsible for both “constitutive” racial pigmentation
and “inducible” pigmentation (the skin’s tanning
response).
Hemoglobin in skin is found within proteins in red blood
corpuscles comprising the rich network of blood vessels
that supply the skin with oxygen. When carrying oxygen
in the blood, hemoglobin takes on a red hue and, as
such, gives young, healthy skin a characteristic, highly
diffuse “bloom” of pink coloration. Deoxygenation of
hemoglobin can produce blue-toned skin coloration.
Collagen is a fibrillar protein that represents some 75
percent of the dry weight of the dermis and provides
both tensile strength and elasticity.6 While it plays an
important structural role, it also contributes significantly to
skin optics. Collagen acts like a mirror, scattering light
back toward the skin surface. As such, it is responsible for
the “brightness” of skin color.
Melanin
Hemoglobin
Collagen
Skin surface
Light
Melanin
Hemoglobin
Collagen
Skin surface
Light
Light reflection and refraction beneath skin’s surface contribute to
outward appearance. With aging, collagen loses its ability to reflect light,
contributing to a dull skin tone.1-5
Young Skin
Aging Skin
2 3
Colored light
diffused softly
by skin surface
Light unevenly
diffused due to
hyperpigmentation
The color of this light is modified by pigments within the skin
Greater than 90%
of light penetrates
Less light penetrates
Skin aging affects texture and pigmentation, creating contrasts on
the face that may be a result of shadows caused by wrinkles or color
changes caused by age spots.
High contrast Low contrast
More contrast created by texture
and pigment in aged skin
Less contrast created by texture
and pigment in young skin
Texture
Texture
Changing with Age
Skin aging research is increasingly revealing how agerelated
changes within the dermal layers impact skin
optics and the appearance of skin tone. Cumulative
changes in the three key skin color chromophores are
among the primary culprits.
In young skin, melanin is evenly distributed, and
melanocyte activity is low, restricted to the production of
constitutive pigmentation only. UV radiation in sunlight
transiently activates melanocytes to produce melanin that
is evenly distributed, as in a tan.
In aging skin, some melanocytes may be damaged by
cumulative UV exposure, causing them to be permanently
“switched on” and overproduce melanin. This overzealous
melanogenesis production can eventually create
permanent local discoloration with sufficient size and
contrast to appear as age spots (lentigines) or as diffuse
hyperpigmentation. As skin turnover decreases with age,
microscopic bits of melanin (“melanin dust”) can become
trapped in the epidermis and stratum corneum,
contributing to a duller appearance.
In young skin, blood vessels in the papillary dermis are
normally delicate structures that are barely visible. Exercise
or hot weather can cause them to dilate, producing an
even, transient increase in red coloration (i.e., “flushing”).
In aging skin, blood vessel walls can be damaged by
repeated exposure to UV sunlight and become
permanently dilated or leaky. This can eventually lead
to discolorations with sufficient contrast to be seen as
“broken veins” and red blotches.15-20 P&G Beauty scientists
have found that the hemoglobin content of skin increases
with age (as measured by an increase in the number of
permanently dilated blood vessels) and the distribution of
hemoglobin in the skin becomes more uneven with age
(as measured by an increase in the number of collections
of dilated blood vessels).15-20 Contrast created by
hemoglobin manifests as “broken” or “spider” veins
(“telangiectasia”) and visible, diffuse red blotchiness.
In young skin, when collagen is in good condition, it is a
highly efficient scatterer, reflecting light back from deep
within the skin to produce a natural glow. As skin ages,
solar UV damages collagen, rendering it unable to reflect
light optimally, not unlike an antique mirror whose glass
is cracked and clouded. Many researchers have found
that the concentration and uniformity of dermal collagen
decreases with age.21-24 P&G Beauty scientists conducted
a study with similar findings by measuring an increase
in the number of areas containing less collagen than
normal.25,26 The effect of these changes is a dull, less
luminous complexion.
Targeting Melanocytes
Recent research advances have helped unravel the
molecular mechanisms that disrupt normal melanin
processing in melanocytes and lead to hyperpigmentation.
Damage to melanocytes can be initiated by UV sunlight
environmental irritants such as pollution, endogenous
hormones, or free radicals (i.e., as a result of UV- or
pollution-induced oxidative stress or released in
inflammatory processes), among other things. All of
these triggers signal the melanocyte to pump out
melanin and ship it off to neighboring keratinocytes.
The schematic (see previous page) shows the known steps
involved in the production of melanin (follow the arrows),
from the transcription of the gene for tyrosinase, to the
activation of tyrosinase by glycosylation, to the transport
of melanosomes out of the cell. Red X’s indicate steps
in the process where melanin production might be
interrupted, along with the known therapeutic strategies
that act mechanistically at each of these “intervention”
points. Combining ingredients that target more than one
mechanism in the process of melanogenesis may provide
greater efficacy in shutting down the melanin factory and
preventing the outward signs of melanin overproduction.
Lab Notes
Getting Under the Skin
The SIAscope is a new state-of-the-art instrument
that uses a unique combination of macro-digital
photography, contact-remittance spectrophotometry
and hyper-spectral imaging to map the concentration
and distribution of chromophores up to 2 mm beneath
the surface of human skin. It has been used for many
years by dermatologists and plastic surgeons to assist
them in identifying and treating a wide range of skin
conditions. P&G Beauty has been working with skinimaging
experts at Astron Clinica to further develop and
refine the SIAscope device to be small, user-friendly and
more broadly available to consumers.
The SIAscope reveals the way light interacts with skin,
specifically, how it is either absorbed by chromophores
or scattered by internal structures. By modeling these
interactions and probing skin with visible and infrared
light, the SIAscope is able to determine the location and
concentrations of light-absorbing and light-scattering
molecules and structures within skin. In particular, this
hand-held instrument is able to rapidly and non-invasively
map melanin, hemoglobin and collagen, the chromophores
that drive human skin coloration and play a
central role in our perception of age, health and beauty.
Examples of chromophore maps of normal human skin
are shown above.
Emotional Attitudes &
Behaviors
The Psychology of Beauty:
Skin Tone Matters!28
Two leading evolutionary biologists, Professor Karl
Grammer and Dr. Bernhard Fink, conducted a unique
study to determine the impact of facial skin tone on the
perception of a woman’s age, health and attractiveness,
independent of facial form and skin texture. To
accomplish this, the scientists created skin color maps
from digital images of women aged 10-70. Facial lines
and wrinkles were removed from each image, leaving skin
color distribution as the only variable.
Using 3-D imaging technology, the scientists applied the
skin color maps to one universal facial structure
(see image). The resulting model faces had identically
shaped features but retained the original women’s skin
color compositions, which were then rated by
participants. The digital images were subsequently
analyzed with the SIAscope technology to determine the
distribution of melanin and hemoglobin chromophores.
The study found:
• Based on age estimates by raters, chromophore
concentration and distribution alone may account
for up to 10-12 years of age perception, independent
of form and skin surface topography.
• There were close correlations between estimated
age and perceived healthiness, and between
estimated age and skin-specific attributes, including
smoothness and firmness.
• There was a strong correlation between age and
melanin homogeneity, suggesting that melanin
distribution drives the majority of tone dependent
age perception.
• Authors concluded that chromophore concentration
and distribution have a major influence on the
perception of female facial age and on judgments
of attractiveness, health and youth.
WHAT WORKS
New Beauty Intelligence
Driven by new understandings about how chromophores
change with age and how these changes affect skin tone
and luminosity, researchers are taking skin care science to
the next level. In particular, an unprecedented view of the
molecular mechanisms that underlie abnormal melanin
production, as detailed in the schematic on page 5, has
enabled scientists to identify and develop therapeutic
compounds that target specific steps in the process to
interrupt melanogenesis and reduce the outward signs of
hyperpigmentation. Two such compounds with proven
effects on age-related changes in chromophores are
niacinamide and glucosamine.
Niacinamide
Niacinamide (also called nicotinamide or
3-pyridinecarboxamide) is the physiologically active
form of niacin, or vitamin B3.30,31 Since it was discovered
and isolated in the late 1930s, it has been linked to a
wide array of dermatological benefits when used as a
topical agent. Recent research has dramatically increased
the understanding of its mechanistic actions and
cutaneous physiological activity including benefits in acne
Niacinamide reduces appearances of spots.34
8 9
Current Topical Ingredients for Treating Hyperpigmentation31
Melanogenesis Inhibitors Key Features
Hydroquinone HQ is current Rx gold standard for depigmentation. Efficacy seen in 2-4 months. Side effects can include
irritation, post inflammatory hyperpigmentation, nail discoloration; rarely hypopigmentation. Difficult
to formulate due to oxidative instability.
N-acetyl Glucosamine N-AG is newest commercially available active identified for hyperpigmentation. Inhibits glycosylation
of pro-tyrosinase. Improvement seen in 4-8 weeks. Effective in both treating and preventing
hyperpigmentation. Very mild and non-irritating in clinical studies.
Vitamin A Derivatives Retinoids reduce pigmentation effectively primarily by reduction of transcription of the tyrosinase gene;
also active exfoliators. Can be irritating. Rx retinoids contraindicated during pregnancy.
Kojic Acid Widely used in Asia. Reduces hyperpigmentation alone or combination with HQ. Side effects can
include allergic contact dermatitis and erythema.
Other: Azealaic Acid, Paper Appear to reduce tyrosinase activity. Studies show at least 19 different traditional Chinese
Mulberry Extract, Aloesin, medicinal herbs inhibit tyrosinase activity in vitro.
Arbutin, Licorice Extract,
Ellagic Acid, Cinnamic Acid,
Sophorcarpidine
Oxidation Inhibition
Ascorbic Acid (Vitamin C), Prevents initiation of the melanogenesis process. Primarily a preventative treatment,
Alpha Tocopherol (Vitamin E), does not treat existing hyperpigmentation. Formulation difficult, as oxygen exposure
Magensium-L-Ascorbyl- reduces efficacy.
2-Phosphate (VC-PMG),
Thiotic Acid (Alpha Lipoic Acid),
Gingko, Ginseng, Pitera
Inhibition of Melanosome Transfer
Niacinamide Down regulates amount of melanosomes transferred from melanocytes to keratinocytes. Other benefits:
barrier improvement, reduced blotchiness, reduced yellowness. Studies show niacinamide synergism with N-AG.
Soybean Trypsin Effective at reducing, preventing pigmentation in vivo. However, efficacy dependent on STI concentration.
Exfoliation
Alpha Hydroxy Acids, Primarily used to treat existing hyperpigmentation by facilitating removal of melanized keratinocytes.
Linoleic Acid, Peels, Can be irritating. High concentrations may cause post-inflammatory hyperpigmentation in darker skin types.
\
improvement and barrier function, and prevention of
photoimmunosuppression and photocarcinogenesis
induced by UV radiation.7,29,30
More recently, niacinamide’s effects on pigmentation,
color and tone have become clear. In published studies,32
an international research team found that niacinamide
inhibits the transfer of melanosomes from melanocytes
to kerotinocytes. The effects of this agent are reversible
as shown in both in vitro and clinical testing;33 however,
it effectively blocks the visual appearance of melanin.
(See melanogenesis figure on page 5.)
Recent clinical data show that a topical preparation
of niacinamide reduces the appearance of hyperpigmented
spots and prevents skin yellowness, as
indicated in the figure that follows. Other evidence
reveals that niacinamide reduces red blotchiness.
Glucosamine/N-acetyl Glucosamine
Well-known for its suggested role in promoting and
maintaining joint health,38 glucosamine is now being
increasingly recognized for its cutaneous benefits when
applied topically. Produced naturally in the body by the
addition of an amino group to glucose, glucosamine
performs a number of key biochemical functions on
its own (e.g., it plays an important role in intercellular
recognition).
N-acetyl glucosamine (N-AG) is an acetylated form of
glucosamine that is more stable when applied topically.
In the skin, research indicates that glucosamine is not a
direct inhibitor of tyrosinase, but rather, it inhibits the
glycosylation of pro-tyrosinase, thereby preventing
its activation and interrupting melanin formation.
(See melanogenesis figure on page 5). Published
research by Mishima and Imokawa has demonstrated
the ability of various glycosylation inhibitors, including
glucosamine, to substantially reduce tyrosinase activity
within cultured melanosomes,39-45 a conclusion also
supported by other data.46,47
To better understand how N-AG influences tyrosinase
activity and melanin content, P&G Beauty scientists
conducted a series of tests on human epidermal
equivalents, which are laboratory-grown, 3-D systems
that include both melanocytes and keratinocytes.
This experimental system enables the measurement
of changes in melanin biosynthesis following topical
administration of compounds of interest. Treating skin
equivalents with topical N-AG for 10 days resulted in a
significant decrease in melanin content.47
In addition, N-AG has been shown to increase collagen
expression in human skin cultures in a dose-responsive
manner.47 Improving collagen leads to smoother skin
texture and a reduction in fine lines and wrinkles,
which, in turn, improves light reflection, diminishes
dullness and results in a more luminous appearance.
Niacinamide/N-AG:
Synergy in Combination
The individual mechanistic effects of niacinamide and
N-AG on pigmentation suggest that combining these
two ingredients may provide even greater cutaneous
benefits, and this hypothesis has proven true based on
a growing body of clinical and in vitro data.
For example, testing in 3-D epidermal equivalents
revealed that a combination of N-AG plus niacinamide,
both in 5% solutions, decreased melanin content by
about 25 percent, a statistically significant (p=<0.05)
improvement over N-AG or niacinamide alone.47
0
5
10
15
20
25
30
Vehicle Control
Niacinamide*
NAG*
Niacinamide + N*
*P < .05
N-AG/Niacinamide Synergistically Reduce Melanin
Both N-AG and niacinamide individually reduce melanin levels in skin
equivalent cultures. Cultures treated with both show a synergistic effect.47
10 11
DID YOU KNOW?
Red in the Face: Niacinamide
Mitigates Blotchiness
Red blotchiness or patches of ruddiness on facial skin
are fairly common dermatological complaints, and
may result from post-acne inflammation, irritation,
aging, UV damage or rosacea.15-20
A growing body of clinical evidence reveals that
niacinamide effectively reduces red blotchiness in
facial skin (see image). A report published in 2004
involving 50 Caucasian females aged 40-60
demonstrated that a 5% topical solution of
niacinamide prevented a seasonal increase in red
blotchiness, confirming results from earlier studies.34
The authors speculated that the documented
improvements in redness may be due to niacinamide’s
demonstrated effects on skin barrier function,
specifically its ability to reduce transepidermal
water loss (TEWL) and increase skin barrier layer
proteins.35,36
In a study of 48 women with stage I/II rosacea,
Draelos et al found that, based on expert
assessment, 96% of the subjects improved
significantly when treated with 2% niacinamide
applied topically for four weeks.37 These clinical
benefits were accompanied by stratum corneum
RESEARCH UPDATE
DEFINING ISSUES
Changing the Tone of Skin Science
In the age-old quest to retain youthful beauty, reducing
wrinkles and fine lines has often overshadowed
maintaining even-toned skin. But a glance at art across
cultures and centuries shows that luminous, even skin
tone is considered ideal. From the palest white powders
used by Japanese courtesans to the bronzers applied by
women of today looking for even, sun-kissed color
without the risk of tanning � changing skin tone to
enhance beauty has been an ongoing interest of women
for hundreds of years. In recent years, medical science
has offered pharmacological tools to help with
pigmentation changes due to natural aging,
photodamage or skin conditions, and many of these
tools and understandings are now being reapplied to the
world of cosmetics. Still, the connection between skin
tone, skin health and perception of age is only beginninge to be illuminated.
New psycho-social research is demonstrating how vital
skin tone is to age and beauty perceptions, and scientists
are gaining new insights into why skin’s luminosity and
uniformity of tone tends to degenerate with age. Using
sophisticated medical imaging tools and computational
models, scientists can now look beneath the surface of
the skin and precisely characterize age-related changes
in sub-surface structure, pigmentation and texture.
As a result of these new understandings and better
research about the underlying biology of pigment
changes, the tone of skin science is changing. Scientists
and dermatologists are beginning to recognize that
repairing tone problems is as important as repairing
texture problems, and are increasingly able to offer
women better and more accessible solutions to achieve
luminous and more even skin tone.
Advances in Science
Defining Tone
The wide range of skin colors – from the deepest
chocolate brown of Africa’s Ivory Coast to the warm
olives of the Mediterranean to the pale fairness of
Scandinavia – is paralleled by a similarly wide array of
cultural beliefs that define “ideal skin tone” in various
geographic regions. Western women may desire the
healthy glow of sun-kissed skin, while Asian cultures
value paleness, sometimes going to great lengths to
lighten skin.
Despite these seemingly contradictory goals, there is one
common quality that seems to define beautiful, desirable
skin the world over: evenness. Regardless of where on the
color spectrum any one individual is, uniform, even-toned
skin has a luminous “lit from within” quality that is
emerging as one of the most critical characteristics of
healthy, youthful attractiveness. Skin texture is also an
important piece of the tone puzzle, because smooth,
fine-textured skin reflects light more evenly.
In the case of both color and texture, contrast seems
to be the key – or more precisely, the lack of contrast.
That’s because the human eye is drawn to edges created
by contrast. Skin aging affects texture and pigmentation,
creating contrasts on the face that may be a result of
shadows caused by wrinkles or color changes caused by
age spots.
Skin tone, then, can be defined as an interplay between
even color and fine texture, both of which act to reduce
contrast and increase luminosity.
Shedding Light on “Skin Optics”
It is said that beauty is in the eye of the beholder and
scientific research has shed new light on precisely how the
human eye processes “beauty” and the roles played by
skin tone and evenness. A rich history of research
on “skin optics” has examined how the reflection and
refraction of light beneath the skin’s surface contributes
to its outward appearance.
Human skin is not a solid, opaque surface. Rather, skin
has depth and layers, and its appearance is determined by
how much light is ultimately reflected back to the eyes.
The amount and color of reflected light is, in turn,
determined by the quality and distribution of lightabsorbing
molecules (chromophores) beneath the stratum
corneum – particularly melanin, hemoglobin and collagen.
(See diagram on opposite page.)
Facial skin normally allows more than 90 percent of light
to penetrate its surface.1-5 White light passing through
skin’s transparent surface is scattered back toward the
surface by dermal collagen, which acts essentially as a
mirror within the skin. The color of this light is modified
by the chromophores, melanin and hemoglobin, both
during its journey into the skin and as it is reflected back
toward the surface. Colored light is then diffused softly at
the surface by the stratum corneum, generating a
luminous glow.
If, however, the delicate, even balance of chromophore
distribution within the skin is disrupted – as can happen
in photoaging or exposure to environmental irritants –
shadowing caused by texture, along with local changes
in pigment concentrations, can dull skin’s luminosity by
creating contrast.
Biological Facts
What Lies Beneath:
The Biology of Tone
The incredible kaleidoscope of human skin color is due to
each individual’s unique dermal concentration and
distribution of skin chromophores, molecules that absorb
or reflect light. While a number of chromophores are
present in human skin, various models of skin optics1-5
indicate that three such molecules – melanin, hemoglobin
and collagen – overwhelmingly drive skin coloration
differences both between different people and within
the same individual.
Melanin is expressed in discrete organelles (melanosomes)
that are assembled within epidermal melanocytes and are
transported, when mature, to neighboring keratinocytes.
Melanin is perceived as a brown-colored pigment,
responsible for both “constitutive” racial pigmentation
and “inducible” pigmentation (the skin’s tanning
response).
Hemoglobin in skin is found within proteins in red blood
corpuscles comprising the rich network of blood vessels
that supply the skin with oxygen. When carrying oxygen
in the blood, hemoglobin takes on a red hue and, as
such, gives young, healthy skin a characteristic, highly
diffuse “bloom” of pink coloration. Deoxygenation of
hemoglobin can produce blue-toned skin coloration.
Collagen is a fibrillar protein that represents some 75
percent of the dry weight of the dermis and provides
both tensile strength and elasticity.6 While it plays an
important structural role, it also contributes significantly to
skin optics. Collagen acts like a mirror, scattering light
back toward the skin surface. As such, it is responsible for
the “brightness” of skin color.
Melanin
Hemoglobin
Collagen
Skin surface
Light
Melanin
Hemoglobin
Collagen
Skin surface
Light
Light reflection and refraction beneath skin’s surface contribute to
outward appearance. With aging, collagen loses its ability to reflect light,
contributing to a dull skin tone.1-5
Young Skin
Aging Skin
2 3
Colored light
diffused softly
by skin surface
Light unevenly
diffused due to
hyperpigmentation
The color of this light is modified by pigments within the skin
Greater than 90%
of light penetrates
Less light penetrates
Skin aging affects texture and pigmentation, creating contrasts on
the face that may be a result of shadows caused by wrinkles or color
changes caused by age spots.
High contrast Low contrast
More contrast created by texture
and pigment in aged skin
Less contrast created by texture
and pigment in young skin
Texture
Texture
Changing with Age
Skin aging research is increasingly revealing how agerelated
changes within the dermal layers impact skin
optics and the appearance of skin tone. Cumulative
changes in the three key skin color chromophores are
among the primary culprits.
In young skin, melanin is evenly distributed, and
melanocyte activity is low, restricted to the production of
constitutive pigmentation only. UV radiation in sunlight
transiently activates melanocytes to produce melanin that
is evenly distributed, as in a tan.
In aging skin, some melanocytes may be damaged by
cumulative UV exposure, causing them to be permanently
“switched on” and overproduce melanin. This overzealous
melanogenesis production can eventually create
permanent local discoloration with sufficient size and
contrast to appear as age spots (lentigines) or as diffuse
hyperpigmentation. As skin turnover decreases with age,
microscopic bits of melanin (“melanin dust”) can become
trapped in the epidermis and stratum corneum,
contributing to a duller appearance.
In young skin, blood vessels in the papillary dermis are
normally delicate structures that are barely visible. Exercise
or hot weather can cause them to dilate, producing an
even, transient increase in red coloration (i.e., “flushing”).
In aging skin, blood vessel walls can be damaged by
repeated exposure to UV sunlight and become
permanently dilated or leaky. This can eventually lead
to discolorations with sufficient contrast to be seen as
“broken veins” and red blotches.15-20 P&G Beauty scientists
have found that the hemoglobin content of skin increases
with age (as measured by an increase in the number of
permanently dilated blood vessels) and the distribution of
hemoglobin in the skin becomes more uneven with age
(as measured by an increase in the number of collections
of dilated blood vessels).15-20 Contrast created by
hemoglobin manifests as “broken” or “spider” veins
(“telangiectasia”) and visible, diffuse red blotchiness.
In young skin, when collagen is in good condition, it is a
highly efficient scatterer, reflecting light back from deep
within the skin to produce a natural glow. As skin ages,
solar UV damages collagen, rendering it unable to reflect
light optimally, not unlike an antique mirror whose glass
is cracked and clouded. Many researchers have found
that the concentration and uniformity of dermal collagen
decreases with age.21-24 P&G Beauty scientists conducted
a study with similar findings by measuring an increase
in the number of areas containing less collagen than
normal.25,26 The effect of these changes is a dull, less
luminous complexion.
Targeting Melanocytes
Recent research advances have helped unravel the
molecular mechanisms that disrupt normal melanin
processing in melanocytes and lead to hyperpigmentation.
Damage to melanocytes can be initiated by UV sunlight
environmental irritants such as pollution, endogenous
hormones, or free radicals (i.e., as a result of UV- or
pollution-induced oxidative stress or released in
inflammatory processes), among other things. All of
these triggers signal the melanocyte to pump out
melanin and ship it off to neighboring keratinocytes.
The schematic (see previous page) shows the known steps
involved in the production of melanin (follow the arrows),
from the transcription of the gene for tyrosinase, to the
activation of tyrosinase by glycosylation, to the transport
of melanosomes out of the cell. Red X’s indicate steps
in the process where melanin production might be
interrupted, along with the known therapeutic strategies
that act mechanistically at each of these “intervention”
points. Combining ingredients that target more than one
mechanism in the process of melanogenesis may provide
greater efficacy in shutting down the melanin factory and
preventing the outward signs of melanin overproduction.
Lab Notes
Getting Under the Skin
The SIAscope is a new state-of-the-art instrument
that uses a unique combination of macro-digital
photography, contact-remittance spectrophotometry
and hyper-spectral imaging to map the concentration
and distribution of chromophores up to 2 mm beneath
the surface of human skin. It has been used for many
years by dermatologists and plastic surgeons to assist
them in identifying and treating a wide range of skin
conditions. P&G Beauty has been working with skinimaging
experts at Astron Clinica to further develop and
refine the SIAscope device to be small, user-friendly and
more broadly available to consumers.
The SIAscope reveals the way light interacts with skin,
specifically, how it is either absorbed by chromophores
or scattered by internal structures. By modeling these
interactions and probing skin with visible and infrared
light, the SIAscope is able to determine the location and
concentrations of light-absorbing and light-scattering
molecules and structures within skin. In particular, this
hand-held instrument is able to rapidly and non-invasively
map melanin, hemoglobin and collagen, the chromophores
that drive human skin coloration and play a
central role in our perception of age, health and beauty.
Examples of chromophore maps of normal human skin
are shown above.
Emotional Attitudes &
Behaviors
The Psychology of Beauty:
Skin Tone Matters!28
Two leading evolutionary biologists, Professor Karl
Grammer and Dr. Bernhard Fink, conducted a unique
study to determine the impact of facial skin tone on the
perception of a woman’s age, health and attractiveness,
independent of facial form and skin texture. To
accomplish this, the scientists created skin color maps
from digital images of women aged 10-70. Facial lines
and wrinkles were removed from each image, leaving skin
color distribution as the only variable.
Using 3-D imaging technology, the scientists applied the
skin color maps to one universal facial structure
(see image). The resulting model faces had identically
shaped features but retained the original women’s skin
color compositions, which were then rated by
participants. The digital images were subsequently
analyzed with the SIAscope technology to determine the
distribution of melanin and hemoglobin chromophores.
The study found:
• Based on age estimates by raters, chromophore
concentration and distribution alone may account
for up to 10-12 years of age perception, independent
of form and skin surface topography.
• There were close correlations between estimated
age and perceived healthiness, and between
estimated age and skin-specific attributes, including
smoothness and firmness.
• There was a strong correlation between age and
melanin homogeneity, suggesting that melanin
distribution drives the majority of tone dependent
age perception.
• Authors concluded that chromophore concentration
and distribution have a major influence on the
perception of female facial age and on judgments
of attractiveness, health and youth.
WHAT WORKS
New Beauty Intelligence
Driven by new understandings about how chromophores
change with age and how these changes affect skin tone
and luminosity, researchers are taking skin care science to
the next level. In particular, an unprecedented view of the
molecular mechanisms that underlie abnormal melanin
production, as detailed in the schematic on page 5, has
enabled scientists to identify and develop therapeutic
compounds that target specific steps in the process to
interrupt melanogenesis and reduce the outward signs of
hyperpigmentation. Two such compounds with proven
effects on age-related changes in chromophores are
niacinamide and glucosamine.
Niacinamide
Niacinamide (also called nicotinamide or
3-pyridinecarboxamide) is the physiologically active
form of niacin, or vitamin B3.30,31 Since it was discovered
and isolated in the late 1930s, it has been linked to a
wide array of dermatological benefits when used as a
topical agent. Recent research has dramatically increased
the understanding of its mechanistic actions and
cutaneous physiological activity including benefits in acne
Niacinamide reduces appearances of spots.34
8 9
Current Topical Ingredients for Treating Hyperpigmentation31
Melanogenesis Inhibitors Key Features
Hydroquinone HQ is current Rx gold standard for depigmentation. Efficacy seen in 2-4 months. Side effects can include
irritation, post inflammatory hyperpigmentation, nail discoloration; rarely hypopigmentation. Difficult
to formulate due to oxidative instability.
N-acetyl Glucosamine N-AG is newest commercially available active identified for hyperpigmentation. Inhibits glycosylation
of pro-tyrosinase. Improvement seen in 4-8 weeks. Effective in both treating and preventing
hyperpigmentation. Very mild and non-irritating in clinical studies.
Vitamin A Derivatives Retinoids reduce pigmentation effectively primarily by reduction of transcription of the tyrosinase gene;
also active exfoliators. Can be irritating. Rx retinoids contraindicated during pregnancy.
Kojic Acid Widely used in Asia. Reduces hyperpigmentation alone or combination with HQ. Side effects can
include allergic contact dermatitis and erythema.
Other: Azealaic Acid, Paper Appear to reduce tyrosinase activity. Studies show at least 19 different traditional Chinese
Mulberry Extract, Aloesin, medicinal herbs inhibit tyrosinase activity in vitro.
Arbutin, Licorice Extract,
Ellagic Acid, Cinnamic Acid,
Sophorcarpidine
Oxidation Inhibition
Ascorbic Acid (Vitamin C), Prevents initiation of the melanogenesis process. Primarily a preventative treatment,
Alpha Tocopherol (Vitamin E), does not treat existing hyperpigmentation. Formulation difficult, as oxygen exposure
Magensium-L-Ascorbyl- reduces efficacy.
2-Phosphate (VC-PMG),
Thiotic Acid (Alpha Lipoic Acid),
Gingko, Ginseng, Pitera
Inhibition of Melanosome Transfer
Niacinamide Down regulates amount of melanosomes transferred from melanocytes to keratinocytes. Other benefits:
barrier improvement, reduced blotchiness, reduced yellowness. Studies show niacinamide synergism with N-AG.
Soybean Trypsin Effective at reducing, preventing pigmentation in vivo. However, efficacy dependent on STI concentration.
Exfoliation
Alpha Hydroxy Acids, Primarily used to treat existing hyperpigmentation by facilitating removal of melanized keratinocytes.
Linoleic Acid, Peels, Can be irritating. High concentrations may cause post-inflammatory hyperpigmentation in darker skin types.
\
improvement and barrier function, and prevention of
photoimmunosuppression and photocarcinogenesis
induced by UV radiation.7,29,30
More recently, niacinamide’s effects on pigmentation,
color and tone have become clear. In published studies,32
an international research team found that niacinamide
inhibits the transfer of melanosomes from melanocytes
to kerotinocytes. The effects of this agent are reversible
as shown in both in vitro and clinical testing;33 however,
it effectively blocks the visual appearance of melanin.
(See melanogenesis figure on page 5.)
Recent clinical data show that a topical preparation
of niacinamide reduces the appearance of hyperpigmented
spots and prevents skin yellowness, as
indicated in the figure that follows. Other evidence
reveals that niacinamide reduces red blotchiness.
Glucosamine/N-acetyl Glucosamine
Well-known for its suggested role in promoting and
maintaining joint health,38 glucosamine is now being
increasingly recognized for its cutaneous benefits when
applied topically. Produced naturally in the body by the
addition of an amino group to glucose, glucosamine
performs a number of key biochemical functions on
its own (e.g., it plays an important role in intercellular
recognition).
N-acetyl glucosamine (N-AG) is an acetylated form of
glucosamine that is more stable when applied topically.
In the skin, research indicates that glucosamine is not a
direct inhibitor of tyrosinase, but rather, it inhibits the
glycosylation of pro-tyrosinase, thereby preventing
its activation and interrupting melanin formation.
(See melanogenesis figure on page 5). Published
research by Mishima and Imokawa has demonstrated
the ability of various glycosylation inhibitors, including
glucosamine, to substantially reduce tyrosinase activity
within cultured melanosomes,39-45 a conclusion also
supported by other data.46,47
To better understand how N-AG influences tyrosinase
activity and melanin content, P&G Beauty scientists
conducted a series of tests on human epidermal
equivalents, which are laboratory-grown, 3-D systems
that include both melanocytes and keratinocytes.
This experimental system enables the measurement
of changes in melanin biosynthesis following topical
administration of compounds of interest. Treating skin
equivalents with topical N-AG for 10 days resulted in a
significant decrease in melanin content.47
In addition, N-AG has been shown to increase collagen
expression in human skin cultures in a dose-responsive
manner.47 Improving collagen leads to smoother skin
texture and a reduction in fine lines and wrinkles,
which, in turn, improves light reflection, diminishes
dullness and results in a more luminous appearance.
Niacinamide/N-AG:
Synergy in Combination
The individual mechanistic effects of niacinamide and
N-AG on pigmentation suggest that combining these
two ingredients may provide even greater cutaneous
benefits, and this hypothesis has proven true based on
a growing body of clinical and in vitro data.
For example, testing in 3-D epidermal equivalents
revealed that a combination of N-AG plus niacinamide,
both in 5% solutions, decreased melanin content by
about 25 percent, a statistically significant (p=<0.05)
improvement over N-AG or niacinamide alone.47
0
5
10
15
20
25
30
Vehicle Control
Niacinamide*
NAG*
Niacinamide + N*
*P < .05
N-AG/Niacinamide Synergistically Reduce Melanin
Both N-AG and niacinamide individually reduce melanin levels in skin
equivalent cultures. Cultures treated with both show a synergistic effect.47
10 11
DID YOU KNOW?
Red in the Face: Niacinamide
Mitigates Blotchiness
Red blotchiness or patches of ruddiness on facial skin
are fairly common dermatological complaints, and
may result from post-acne inflammation, irritation,
aging, UV damage or rosacea.15-20
A growing body of clinical evidence reveals that
niacinamide effectively reduces red blotchiness in
facial skin (see image). A report published in 2004
involving 50 Caucasian females aged 40-60
demonstrated that a 5% topical solution of
niacinamide prevented a seasonal increase in red
blotchiness, confirming results from earlier studies.34
The authors speculated that the documented
improvements in redness may be due to niacinamide’s
demonstrated effects on skin barrier function,
specifically its ability to reduce transepidermal
water loss (TEWL) and increase skin barrier layer
proteins.35,36
In a study of 48 women with stage I/II rosacea,
Draelos et al found that, based on expert
assessment, 96% of the subjects improved
significantly when treated with 2% niacinamide
applied topically for four weeks.37 These clinical
benefits were accompanied by stratum corneum
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