|Year : 2007 | Volume
| Issue : 2 | Page : 71-77
|Changing skin color: Evolution and modern trends
N Radhakrishnan, K Vijayachandra, S Ranganathan
CavinKare Research Center, No. 12 Poonamallee Road, Ekkattuthangal, Chennai - 600 097, India
CavinKare Research Center, No. 12, Poonamallee Road, Ekkattuthangal, Chennai - 600 097
Source of Support: None, Conflict of Interest: None
| Abstract|| |
The present article reviews various evolutionary events that resulted in skin color variation among humans. Skin of the early man is presumed to be colorless as that of the chimpanzees. During the course of evolution, hairless state of skin with sweat glands would have occurred for the purpose of thermoregulation. Thermoregulation was very important for brain development and function. In due course, pigmentation occurred in the naked skin of man in order to offer photo-protection. The physiological demand of vitamin D 3 and folate in human system and the effect of sun-light in their synthesis and metabolism would have further established some changes in the skin color of man in various geographic locations. Although genetics and physiological adaptations have determined human skin color in different groups/races, during the course of civilization, humans have developed a deep desire to change skin color. Current scientific research on development of novel agents for modulation of skin color is likely to benefit in pigmentary disorders and also in psychological well being through the use of cosmetics.
Keywords: Cosmetics, folate, human skin color, melanotoxicity, MSH, photoprotection, tyrosinase, vitamin D 3
|How to cite this article:|
Radhakrishnan N, Vijayachandra K, Ranganathan S. Changing skin color: Evolution and modern trends. Indian J Dermatol 2007;52:71-7
|How to cite this URL:|
Radhakrishnan N, Vijayachandra K, Ranganathan S. Changing skin color: Evolution and modern trends. Indian J Dermatol [serial online] 2007 [cited 2020 Apr 8];52:71-7. Available from: http://www.e-ijd.org/text.asp?2007/52/2/71/33282
Skin, the finest covering of the body, functions as an active biological barrier separating the internal homeostasis from the environment outside. Skin protects our internal organs and system from harsh environment by functioning as a barrier to microbes, chemicals and ultra-violet radiation found in the sunlight and also prevents water loss. A remarkable diversity in structure and function of the skin is seen, depending upon the anatomic site and influence of the environment. The color and texture of the skin plays a major role in the appearance of an individual as 'beauty is nothing but skin deep'. Undesirable skin pigmentation can be the natural dark or light color or can be due to photo-induced ageing (freckles, solar lentigines), hormonal disorders like melasma and chloasma (due to contraceptives, pregnancy, menopause) and irritation of skin or inflammatory reactions and autoimmune condition like vitiligo. When the pigmentation is not uniform, unattractive marks appear on the skin that may require treatments and can be achieved through pharmaceuticals/clinical procedures or by use of cosmetic products. The most important determinant of color of the human skin is the pigment melanin synthesized by melanocytes in the skin.  In addition to melanin (brown), blood flow (red oxygenated hemoglobin and blue reduced hemoglobin) and β -carotene (yellow) content of skin also determines color of skin.  This review focuses on human skin color variation, its evolution and modulation using cosmetics.
| Evolution of Human Skin Color|| |
In mammals (excluding humans), the color of skin/fur plays an important role in camouflage and prey-predator relationship. The striped zebra or long necked giraffe shows high level of camouflage due to their fur color. This is true with the big cats as well. The bear with varied fur coloration according to various geographic locations also explains the above statement.  However, ecological adaptation for camouflaging is not a well-accepted theory at least in human skin coloration. According to Post et al. ,  the skin coloration of early humans is considered to be similar to that of our closest living relatives, the chimpanzees, being white or lightly pigmented and covered with dark hair. The color of the skin in the exposed areas in a chimpanzee, especially in the facial region, varies considerably, the facial skin of the chimpanzee being dark with age and also due to UV exposure. In general, the epidermis of most of the non-human primates is non-pigmented due to the absence of active melanocytes in the epidermis, suggesting that this is the normal skin coloration of primates. On the contrary, pigmentation in the exposed and hairless area of the skin in these primates indicates that the pigmentation is due to exposure to sun-light. 
Evolution of hairless state in the skin is closely linked with the changes in the sweat gland distribution pattern.  During the course of evolution, the critical function of the integument (skin) was maintained through an increased number of sweat glands, particularly in the facial region.  This helps in enhancing the rate of evaporative cooling. The brain is extremely sensitive to temperature. The brain expansion and increased activity required high level of cooling to maintain the temperature. Naked skin affords thermoregulatory advantage.  The hairless state of skin is evolved in order to facilitate thermoregulation through an increased number of sweat gland formation. However this creates a special need for protection of sub-epidermal tissue against UV. This protection was accomplished by an increase in melanization of the skin. This theory clearly put forth that the pigmentation of the skin has occurred mainly for the purpose of photo-protection. This theory is most accepted among various theories on human skin color variation.
Among several mechanisms suggested to provide a selective advantage for dark skin in conditions under high UV irradiation, the most tenable is protection from sunburn and skin cancer due to the physical barrier imposed by the epidermal melanin. The above theory was further supported by the study on the role of light in human skin color variations by Quevedo et al .  This theory states that the constitutive skin color in man designates the genetically-determined levels of melanin pigmentation developed in the absence of exposure to solar radiation or other environmental influences which is seen in the case of neonates, whereas, the facultative skin color or tan, characterizes the increase in melanin pigmentation above the constitutive level induced by the UV. Their studies clearly reveals how tanning (melanization) occur during sun exposure for the purpose of photo protection.
Fitzpatrick in the year 1988 offered greater sanctity to the above theory of melanization for the purpose of photo-protection.  He has classified the skin into VI types based on the photosensitivity pattern.[Table - 4]
The study of Gregory Barsh in 2003  correlating the skin color with latitude has proved that darker skin color in humans is seen in equatorial proximity. Further the study found that the skin reflectance is lowest at the equator and then gradually increases about 8% per 10º of latitude in Northern Hemisphere and 4% per 10º of latitude in Southern Hemisphere. This pattern is inversely correlated with levels of UV irradiation, which are greater in southern hemisphere than in the northern hemisphere. But we do not know how this skin color variation along the latitude is correlated with the change in pattern of UV irradiation over time and also we do not know when did the changes in skin color evolve with multiple migration out of Africa with extensive genetic interchange over 50,000 years.  Most anthropologists accept the notion that differences in UV irradiation have driven selection for dark human skin at the equator and for light skin at greater latitudes. What remains controversial is the mechanism of selection.
The most popular theory affirms the fact that the protection offered by dark skin from UV irradiation becomes a liability in more polar latitudes due to vitamin D 3 deficiency. On sun exposure, 7-dehydrochlolesterol in the skin gets converted to previtamin D 3 and subsequent to that vitamin D 3 at body temperature.  Increased level of melanin in the skin necessitates a prolonged exposure to UV to synthesize an adequate amount of previtamin D 3 . Deeply melanized skin becomes a burden and non-adaptative for the above purpose. Vitamin D 3 is essential for normal growth, calcium absorption and skeletal development. Deficiency of the vitamin can cause death, immobilization or pelvic deformities.  Vitamin D 3 is very essential during pregnancy and lactation because of the need for enhanced maternal absorption of calcium in order to build the fetal and neonatal skeletal system. It has been reported that the migrants from Ethiopia to Israel or from Indian sub-continent to urban centers of Europe are at risk of vitamin D 3 deficiency and its manifestations.  Depigmentation of the skin was a necessary adaptation for humans to inhabit outside tropics. It was argued that deeply pigmented skin was also an adaptation for physiological regulation of vitamin D 3 levels. Highly pigmented skin prevents UV radiation induced vitamin D 3 toxicity caused by over-synthesis of previtamin D 3 . However many challenged this postulate as vitamin D 3 toxicity is prevented by photolysis.  Vitamin D 3 toxicity can occur as a result of systemic overdosing of the vitamin and no single case of naturally occurring vitamin D 3 toxicity as a result of sun exposure has ever been reported.  Many challenged the requirement of prolonged sun exposure for vitamin D3 synthesis. The winter in Europe is very cold and long and hence the spring and summer must afford good opportunity for UV exposure. The long dull winter in Europe would not cause vitamin D 3 deficiency, as the vitamin D 3 can be stored in fat and muscle.
Another theory linked to skin color variation is folate metabolism. The folate is very sensitive to UV radiation. It has been proved that photolysis of the folate occurs in humans when the serum or light-skinned subjects were exposed to simulated natural sun light.  Folic acid is an essential nutrient, which is required for nucleotide and therefore DNA synthesis.  Folate deficiency may lead to macrocystic megaloblastic anemia, bone marrow maturation and impaired development of red blood cells. In non-human primates, folate deficiency is known to produce fetal abnormalities and multiple organ malformation.  Further, it has also been established that there is connection between folate metabolism and neural tube defects (NTDs) in humans.  The records in developed countries show that anencephalus and spina bifida were common in light skinned populations. These defects caused about 15% of all perinatal and 10% of postperinatal mortality in the worst affected populations before introduction of preventive nutritional supplementation.  Folic acid prevents 70% of NTDs in humans. Besides this, folate is also very essential for reproduction and spermatogenesis. Highly melanized integument is established to protect the folate photolysis in individuals of marginal nutritional status.
Human skin color variation is highly adaptative and has evolved for the physiological needs of humans inhabited in regions of varying sun exposure. The selective pressure of photo protection, vitamin D 3 synthesis and protection of folate has created two lines of skin pigmentation. From equator to the poles, the skin pigmentation has evolved mainly for photo-protection. Deeply melanized skin protects against folate photolysis and helps to prevent UV induced damage. The second line of lighter pigmentation at 30° N to the North Pole has occurred with a clear purpose of maximizing vitamin D 3 synthesis as this region experiences very low sunlight. Humans inhabiting at intersection of these lines demonstrate a potential for developing varying degrees of facultative pigmentation (tanning). 
The skin pigmentation is relatively labile and can adapt to local conditions over relatively short periods of geological time. Some human lineages through time may have gone through alternating periods of depigmentation and pigmentation as they moved from one region to other (and vice-versa ). Due to the fast migration in recent times, the poor skin color adaptation has been seen in these recent migrants such as English population to Australia in 19 th and 20 th century, Indians and Pakistanis moved to England in recent decades.  Although the adaptative changes in the skin color seen in humans across the globe may offer very little to the phylogenetic research, it has been of very great value to survive in the particular ecosystem.
| Mechanism of Melanin Biosynthesis|| |
The color of the skin, be it black or white, has always captured the attention of the mankind. The mention about various skin color changes was well-documented in almost all the traditional literatures of the world. However, the mechanism involved in such change was not clearly known. Sangiovanni in 1819 was the first to describe pigment cells, which he referred as 'chromatophores'. Later on, Ehrmann and Meyerson coined the terms 'melanin' and 'melanoblast'. Subsequent to that, Henle in 1837 identified the pigment producing cells in human epidermis.  With the discovery of melanin and melanocytes, the focus of research turned towards understanding the mechanism involved in pigmentation.
Melanin the major skin color determining pigment is synthesized by a specialized dendritic cells called melanocytes. In the skin, melanocytes are found in the epidermal layer, interspersed between keratinocytes and in hair follicles. Melanocytes synthesize melanin in organelles called melanosomes and later they transfer these melanosomes to keratinocytes.  The mechanism of melanosome transfer to keratinocytes is not well understood. However, four different processes have been proposed for the transfer of melanosomes from melanocytes to keratinocytes: 1. Cytophagocytosis. 2. Release of melanosomes from melanocytes to intercellular space, followed by endocytosis of melanosomes by keratinocytes. 3. Transfer of melanosomes through a communication between melanocytes and keratinocytes. 4. Inoculation of melanosomes by melanocytes into keratinocytes. , After the melanosomes are transferred to keratinocytes, melanosomes are packaged in secondary lysosomes that contain acid phosphatase.  Once redistributed in the keratinocytes, melanosomes are degraded by lysosomes. This melanin protects the nucleus from UV light and offers a very visible skin color to the keratinocytes.
Melanin is a complex polymer of indolequinone and/or dihydroxyindole carboxylic acid. Based on the structural difference, two kinds of melanins have been identified i.e., black or brown colored eumelanin and reddish-brown pheomelanin. Pheomelanin polymer contains additional cysteine residues. The aminoacid tyrosine is the precursor for the synthesis of melanin. The enzyme tyrosinase initiates a multistep melanin synthesis reaction in melanosomes [Figure - 1]. Tyrosinase, a copper containing transmembrane glycoprotein, is the rate-limiting enzyme in the melanin biosynthesis pathway. Tyrosinase is a trifunctional enzyme that catalyzes hydroxylation of aminoacid tyrosine to 3,4-dihydroxy-phenylalanine (DOPA), the oxidation of DOPA to DOPA-quinone and oxidation of 5,6-dihydroxyindole to indole-5,6-quinone.  TYRP2, encoded by slaty locus, functions as DOPA-chrome tautomerase.  TYRP1, encoded by brown locus, functions as 5,6-dihydroxyindole-2-carboxylic acid oxidase.  Tyrosinase is required for both eumelanin and pheomelanin synthesis, whereas TYRP1 and TYRP2 are required only for eumelanin synthesis. Synthesis of pheomelanin involves addition of cysteine to DOPA-quinone, subsequent cyclization of cysteinyl DOPA and further polymerization.
| Cosmetics for Color Modulation|| |
Humans are always fascinated by color and appearance of the skin and the hair. Men and women always harbor a hidden desire to change their skin and hair color. Fair-skinned people take different routes to tan their skin whereas darker skinned people, on the contrary, try to lighten/whiten their skin. So altering the skin color becomes a very important area of research especially in the cosmetic industry. Most of the skin-lightening cosmetic products contain ingredients to inhibit melanogenesis and also sunscreens to block UV radiation. On the other hand, the tanning is usually done by sun exposure or by using dihydroxyacetone in sunless tanning products.  In addition, α-melanocyte stimulating hormone (α-MSH) mimicking peptides are also used as an alternative to sun tanning.  Although hyperpigmention disorders like melasma, freckles and senile lentigenes and hypopigmentation disorders like vitiligo are quite common, this review does not deal with these disorders and their treatment by skin color modulation.
| Cosmetic Ingredients for Skin-lightening|| |
Although several skin-lightening ingredients are available, either they have mediocre effect on skin pigmentation or have toxic effects. Hydroquinone is a compound not commonly used in cosmetics but is highly effective in skin lightening and used as a drug in many countries. Skin-lightening formulations usually contain sunscreens (blocking UV) as well as inhibitors of melanin levels in the epidermis. Different strategies used for reduction of melanin content in the epidermis are inhibition of tyrosinase, inhibition of melanosome transfer from melanocytes to keratinocytes and inhibition of α-melanocyte stimulating hormone (α-MSH). Commonly used ingredients for skin-lightening have been summarized [Table - 1]. [Table - 2] and [Table - 3] highlight some of the fairness creams available and new actives and mechanism of fairness respectively.
Sunscreens that block UV exposure of skin are the only cosmetic products generally accepted and recommended by dermatologists. In addition to preventing darkening of skin by sun exposure, sunscreens also prevent or delay skin cancers that may occur due to constant sun exposure. 
Harmful effects of ultraviolet (UV) radiation include DNA damage, immunosuppression and hyperpigmentation. Sunlight has three UV components - UVA (320-400 nm), UVB (280-320 nm) and UVC (100-280 nm). In the atmosphere oxygen and ozone absorb most of UVC and 90% of UVB. We get exposed only to UVA and UVB when we go out during daytime. UVB is strongest in summer when earth is closest to sun. In the winter when the earth rotates away from the sun, UVB does not reach the surface of earth. UVA reaches earth with the same strength in both winter and summer. UVB has the strength to penetrate only the epidermis whereas UVA can reach the dermis also. UVB stimulates melanocytes to produce more melanin. UVA is a strong oxidant and overexposure to sunlight induces inflammatory response in the skin, which acutely manifests as erythema or sunburn. UVA has a bigger impact on oxidative stress in the skin than UVB by inducing reactive oxygen and nitrogen species that damage DNA, proteins and lipids. UVA induces hyperpigmentation immediately whereas UVB causes delayed hyperpigmentation. Several UV filters are available for incorporation into sunscreen formulations.  Sunscreens are either physical sunscreens (physical blockers) or organic sunscreens (chemical absorbers). Physical sunscreens are chemicals that reflect or scatter the ultraviolet radiation. Physical sunscreens like titanium dioxide (TiO 2 ) attenuate the effect of UVB and zinc oxide (ZnO) attenuate the effect of UVA. Organic sunscreens absorb the harmful UV radiation. UVA absorbers are chemicals that absorb radiation in the 320 to 360 nm regions of spectrum (benzophenone, anthranilates and dibenzoyl methanes). UVB absorbers are the chemicals that absorb radiation in the 290 to 320 nm region of the spectrum (para-aminobenzoic acid derivatives, salicylates, cinnamates and camphor derivatives). Sunscreen formulations usually contain physical blockers as well as UVA and UVB absorbers and prevent the skin from tanning. Sunscreens also protect people from sunburn and milder forms of cancer, squamous cell and basal cell carcinoma. But sunscreens do not provide protection against melanoma. 
Because of its critical role in melanin biosynthesis, the enzyme tyrosinase has become a major target for inhibition in skin-lightening cosmetics. Hydroquinone is one of the most popular depigmenting agents and is used extensively to treat several hyperpigmentation disorders. Depigmentation by hydroquinone is because of its ability to inhibit tyrosinase as well as cytotoxicity to melanocytes. Melanotoxicity of hydroquinone is independent of cellular melanin content but requires the presence of active tyrosinase enzyme. However, because of the carcinogenic properties, use of hydroquinone is banned or limited in cosmetic products in many countries. One of the requirements for the enzymatic activity of tyrosinase is copper in its active site. Depletion of copper by copper-chelators like kojic acid, methyl gentisate or ellagic acid inhibits tyrosinase activity. Kojic acid is a popular ingredient used in skin-lightening cosmetics. However, because of its mutagenicity, the use of kojic acid in cosmetics is banned in Japan. Other popular tyrosinase inhibitors used in cosmetics are natural compounds like glabridin and arbutin.  Extracts from plants like licorice ( Glycyrrhiza glabra ), paper mulberry ( Morus ) and Rumex extracts are also known to inhibit tyrosinase and are used extensively in skin-lightening cosmetic products. ,
Melanosome transfer inhibitors
The skin gets its color only after the transfer of melanosomes from melanocytes to keratinocytes in the epidermis and by obstructing this process, the skin color can be lightened.  A serine protease inhibitor RWJ-50353 was shown to inhibit transfer of melanosomes from melanocytes to keratinocytes resulting in depigmentation.  Niacinamide (vitamin B 3 ) is a popular ingredient in skin-lightening cosmetics, which inhibits melanosome transfer from melanocytes to keratinocytes resulting in lighter skin colour.  Another inhibitor of melanosome transfer is soy extract. Soy extract contains two proteins, soybean trypsin inhibitor and Bowman-Birk inhibitor that act through Par-2 protein, a phagocytic receptor expressed on keratinocytes. Inhibition of Par-2 pathway decreases the rate of transfer of melanosomes to keratinocytes, resulting in skin- lightening.  The ability of soybean trypsin inhibitor, Bowman-Birk inhibitor and soy milk in depigmentation and prevention of UV induced pigmentation, correlate with Par-2 protein cleavage, with cytoskeletal and cell surface reorganization and with reduced keratinocyte phagocytosis. 
α-MSH is a hormone that binds to MC1R receptor, a G-protein coupled receptor on melanocytes and activates it. α-MSH on binding to MC1R receptor, stimulates adenylate cyclase, which increases the intracellular levels of cAMP. This results in increased tyrosinase activity through increased tyrosinase mRNA and protein levels, leading to the induction of melanogenesis. Inhibition of α-MSH results in skin lightening. Several peptide inhibitors have been developed for inhibition of α-MSH to be used as ingredients in skin lightening cosmetics.  Senkyunolide A (3-butyl 6,7-dihydrophthalide), a naturally occurring phthalide extracted from Ligusticum chuanxiong or Cnidium officinale was found to be an α-MSH inhibitor with skin-whitening activity. 
| Conclusions|| |
The color of the human skin has kept changing during the course of evolution and in different geographic locations due to physiological adaptation. Changing skin colors have helped humans to thrive better in their new environments. Modulation of skin color is essential in case of pathological conditions like hypo and hyper pigmentation. In some situations like tanning for cosmetic purpose that may lead to skin cancer, there is a need to exercise caution before venturing into extreme skin color change. Both pharmaceutical and cosmetic industries are in pursuit of better ingredients for lightening or darkening skin color. Progress made in understanding melanogenesis and its modulation by both pharmaceutical as well as cosmetic industries will contribute to this field. In many cases, cosmetic modulation of skin color helps in psychological wellbeing. Most of these products offer reversible changes and do not interfere in the adaptative changes of the skin to the environment.
| Acknowledgment|| |
We thank Mr. C. K. Ranganathan, CMD, CavinKare Pvt, Ltd., for his interest and encouragement. We would like to thank Dr. T. Mukhopadhyay, Vice-President (R and D) for useful discussions during the preparation of the manuscript. We acknowledge Mr. G. D. Rajesh and Mr J. Kasinathan for their help in preparing the diagram and getting some valuable reprints.
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[Figure - 1]
[Table - 1], [Table - 2], [Table - 3], [Table - 4]
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