The ingredients used for facial skin whitening activate biological processes that are intended to reduce or eliminate the production of melanin.

There are several means of achieving this reduction:

• Inhibit tyrosinase synthesis
• Use complex copper that inhibits tyrosinase function
• Eliminate oxidation reactions that lead to the formation of melanin
• Slow down the transfer of melanosomes to keratinocytes
• Act upstream on the hormone that stimulates melanogenesis (MSH)

Most of the depigmenting agents currently on the market decrease melanogenesis by inhibiting tyrosinase activity in the melanocytes as well as by inhibiting melanosome maturation using one of the mechanisms described in the blog ‘Facial Skin Whitening’.

Hydroquinone

In the past hydroquinone was the main active ingredient used in facial skin whitening treatments, and it was thought to be safe and effective for skin lightening. However, several clinical studies concluded that there may be side effects associated with the long-term use of hydroquinone- there were reports of possible carcinogenicity and a link to ochronosis. As a result, the FDA withdrew the 1982 TFM for OTC skin bleaching drug products containing hydroquinone.  Since the banning of hydroquinone from the OTC market, there has been a growing demand for an alternative natural, safe, and efficacious de-pigmenting treatment.

Ascorbic acid (vitamin C)

Vitamin C can be found in a few different forms, but ascorbic acid is the most biologically active and effective form.

Ascorbic acid is a key ingredient in many physiological functions in the human body.  It is a powerful antioxidant since it donates electrons and prevents oxidation by keeping iron and copper atoms in their reduced states.

The physiological functions of Ascorbic acid include the synthesis of:

• Collagen
• Carnitine
• Neurotransmitters
• Tyrosine

Collagen production is crucial for repairing damaged facial tissue.  Clinical studies have shown that the skin heals faster and scars less when it is infused with vitamin C. Thus, Ascorbic acid is used to stimulate collagen production which results in smoother and more supple skin.

Ascorbic acid whitens facial skin by inhibiting the production of tyrosinase, which reduces the production of melanin. It also protects the skin from harmful damage caused by sun exposure.  Excessive exposure to sunlight, especially UV rays, creates reactive oxygen species in the skin that provoke skin damage. Vitamin C significantly reduces the impact of these reactive oxygen species by donating electrons which neutralize them.

With so many facial skin benefits, it is not surprising that there is an abundance of topical products (creams, gels, serums) containing vitamin C on the market. The products claim to treat a wide variety of skin conditions- from facial skin whitening to fine line and wrinkle reduction . However, it is critical to know that when applied topically, the efficacy of ascorbic acid is very small and often non-existent.  This is due to the fact that vitamin C (C₆H₈O₆) is a very unstable molecule which degrades once it is exposed to light, and as soon as it degrades, it loses all of the benefits described above.

It is easy to detect the degradation of the vitamin C since it turns a yellow-brown color upon degradation. Cosmetic products that claim to have vitamin C as an active ingredient, and which are colored yellow-brown, are misleading consumers since in actual fact the vitamin C in these products has lost its skin rejuvenation properties and is an inactive, degraded, vitamin C.

The structure of the skin is another factor which greatly reduces the effectiveness of cosmetics containing vitamin C. The upper layer of the skin, the stratum corneum, protects the deeper layers of the skin by rejecting materials that attempt to penetrate it. Vitamin C is a hydrophilic molecule which easily dissolves in water, while the stratum corneum is hydrophilic, meaning it is water resistant. Therefore, to effectively penetrate vitamin C into the skin, it is essential to first exfoliate the stratum corneum.

Kojic acid

For over 30 years, Kojic acid has been used as a facial skin whitening agent. Kojic acid, like hydroquinone, prevents the formation of dopachrome – an intermediate stage in the biosynthesis of melanin. Kojic acid is obtained by the fermentation of a strain of Aspergillus orizae.

Since hydroquinone and its esters have been banned in several countries, Kojic acid has been used to replace it. Kojic acid at 1% concentration has bleaching properties,  but when it is used, it immediately turns the cosmetic emulsion yellow and within four to six weeks it turns it brown.  Furthermore, its acidity is very weak since it is linked only to the presence of a hydroxyl function in the molecule. Additionally, it is unstable since it is very sensitive to heat (above 40°C) and oxidizes easily.  Therefore, it must be added into emulsions when they are cooled and needs to be combined with antioxidants such as ascorbic acid (vitamin C).

Although relatively safe and effective, recent studies have shown that it is responsible for skin irritation, sensitization and in rare cases where it has been frequently used, it has been related to contact dermatitis.

In Japan, the country where Kojic acid was first used for skin bleaching, the product isn’t banned, but the authorities have stated that they don’t want new formulations to include the acid.

Niacinamide or nicotinamide or vitamin B3

Another way to achieve skin lightening is to limit the transfer of pigment into the skin cells. Niacinamide (vitamin B3) and Soy are primary nutrients which affect the transfer of melanosome and thus pigmentation.

Niacinamide (nicotinamide) is an effective skin lightener, especially for skin conditions in which hyperpigmentation may occur on the face or other visible parts of the body. Niacinamide has been found to reduce hyperpigmentation in a pigmented reconstructed epidermal (PREP) model by inhibiting 35-68% of melanosome transfer from melanocytes to keratinocytes. It inhibits melanosome transfer without affecting tyrosinase activity, melanin production, melanocyte number or cell viability. The melanosome transfer is modulated by protease-activated receptor 2 activation (PAR-2) leading to disrupted keratinocyte phagocytosis. Most importantly, Niacinamide inhibits the transfer of melanosomes to keratinocytes without affecting the activity of tyrosinase.

Alpha-Hydroxy Acids

A very popular method for lightening the skin uses alpha hydroxyl acids (AHA).  AHA is a natural ingredient that effectively exfoliates the skin and also helps with hyperpigmentation by speeding up skin’s natural cell turnover – known as Skin Turnover Acceleration

L(+) lactic acid is part of the alpha hydroxyl acids (AHA) group. It is known to stimulate the desquamation process which increases the skin’s cell renewal rate. This not only results in smoother skin and the disappearance of fine lines, but also causes melanogenic suppression or skin whitening activity (as a result of the suppression of the formation of tyrosinase). The product needs to be formulated at lower pH levels to speed up the cell renewal.

The use of lactic acid and other lactates in skin lightening products has multiple benefits such as moisturization, increase of the skin’s ceramide level and skin lightening.

Introduction

More than ever before, there is a huge emphasis in the beauty market on skin tone.  Customers the world over are seeking effective products that will even out their skin tone, and many individuals with darker skin are looking for skin whitening products.

The desire to use skin whitening products varies considerably between cultures. Hyperpigmentation is the most common and distressing condition afflicting people in Western countries.  These individuals often seek to eliminate localized hyperpigmentation as well as to lighten their skin tone in general.  In Asian countries, skin whitening products are mainly used to achieve a whiter and brighter facial skin tone.

The main purpose of facial skin whitening products is to lighten the skin as well as even out the skin tone.  It is also used to treat pigmentation disorders such as blemishes, pregnancy marks and age spots.

The active ingredients in the facial skin whitening creams work in two ways:

• By absorbing the UV rays, thus preventing the sun damaging and darkening the facial skin.
• By reducing the production of melanin, the pigment found in the skin which is responsible for skin color and darkening.

Facial Skin Pigmentation

Dermal melanin is produced by melanocytes, cells that are located at the bottom layer of the skin. The type and amount of melanin synthesized by the melanocyte and its distribution pattern in the epidermis determines the actual color of the facial skin.

Melanin comes in two forms: pheomelanin and eumelanin. These two forms are found in facial skin and hair. Eumelanin is the form which mostly determines the skin color due to its high concentrations (i.e. the higher the concentration of eumelanin, the darker the skin tone).

All skin types also have pheomelanin in the skin and hair. Pheomelanin is responsible for creating pink to red hues in the skin and is found in high concentrations in red hair as well as in lips, nipples, glans of the penis and vagina.

Some research has stated that pheomelanin may become carcinogenic if exposed to UV light.

Facial Skin Pigmentation Mechanism

Melanin in melanocytes form due to a series of oxidative reactions involving tyrosine and the enzyme tyrosinase.

Eumelanin is formed from the amino acid tyrosine, when it is acted upon by the enzyme tyrosinase, which itself is dependent on its co-enzyme copper. A succession of oxidation reactions leads to the formation of indole-5,6-quinone, and then the colored polymer. This synthesis takes place in the melanosomes, cellular organelles that extend from the melanocytes, which are transferred to keratinocytes that migrate from the basal layer of the epidermis to the stratum corneum.

Melanin forms through a series of oxidative reactions involving the amino acid tyrosine and the enzyme tyrosinase.

Tyrosinase catalyzes three different reactions in the biosynthetic pathway of melanin in melanocytes: the hydroxylation of tyrosine to l-DOPA and the oxidation of l-DOPA to dopaquinone; furthermore, in humans, dopaquinone is converted by a series of complex reactions to melanin.

The first step is the most critical because the remainder of the reaction sequence can proceed spontaneously at physiological pH. Here, tyrosinase converts tyrosine to dihydroxyphenylalanine (DOPA) and then to dopaquinone. Subsequently, dopaquinone is converted to dopachrome through auto-oxidation, and finally to dihydroxyindole or dihydroxyindole-2-carboxylic acid (DHICA) to form eumelanin (black-brown pigment). The latter reaction occurs in the presence of dopachrome tautomerase and DHICA oxidase. In the presence of cysteine or glutathione, dopaquinone is converted to cysteinyl DOPA or glutathione DOPA. Subsequently, pheomelanin, a yellow-red pigment, is formed.

There are several means of reducing or eliminating melanin formation:

• Inhibit tyrosinase synthesis
• Complex copper to inhibit tyrosinase function
• Eliminate oxidation reactions that lead to the polymer formation
• Slow down the transfer of melanosomes to keratinocytes
• Act upstream on the hormone that stimulates melanogenesis

Most of the depigmenting agents presently on the market decrease melanogenesis by inhibiting tyrosinase activity in melanocytes as well as by inhibiting melanosome maturation by one or other of the mechanisms described.

In the next blog some of the most popular active ingredient for facial skin whitening will be presented.