Skin Whitening Agents. Many agents have been shown to be effective in skin whitening; some have beneficial side effects (e.g.: are antioxidants, nutrients, or decrease the risk of some types of cancer); some are a significant risk to health (for example, those containing mercury).
Pre-melanin synthesis Skin Whitening Agents
Tretinoin is an skin whitening agent which is as pre-melanin synthesis of skin whitening agents. Research has shown that the use of tretinoin (also known as all-trans retinoic acid) can only be somewhat effective in treating skin discolorations. Users of tretinoin have to avoid sunlight, as the skin can tan. Using tretinoin always makes the skin more sensitive to UVA and UVB rays.
During melanin synthesis Skin Whitening Agents
In skin whitening agents, hydroquinone is one of them. In medical literature, hydroquinone is considered the primary topical ingredient for inhibiting melanin production. Its components have potent antioxidant abilities. Topical hydroquinone comes in 2% (available in cosmetics, often as monobenzone) to 4% (or more) concentrations (available from a physician or by prescription), alone or in combination with tretinoin 0.05% to 0.1%. Research has shown hydroquinone and tretinoin to prevent sun- or hormone-induced melasma.
Where it was banned?
Hydroquinone is a strong inhibitor of melanin production, meaning that it prevents dark skin from making the substance responsible for skin color. Hydroquinone does not bleach the skin but lightens it, and can only disrupt the synthesis and production of melanin hyperpigmentation. It has been banned in some European countries (e.g. France) because of fears of a cancer risk. However, other European countries (e.g. Spain) have both prescription and nonprescription formulations.
Is Hydroquinone safe?
Some concerns about hydroquinone’s safety on skin have been expressed, but the research when it comes to topical application indicates negative reactions are minor or a result of using extremely high concentrations or from other skin-lightening agents such as glucocorticoids or mercury iodine. Any perceived risk is most likely applicable for African women. Hydroquinone has been shown to cause leukemia in mice and other animals. The European Union banned it from cosmetics in 2001, but it shows up in bootleg creams in the developing world. It is sold in the United States as an over-the-counter drug, but with a concentration of hydroquinone not exceeding 2 percent.
Because of hydroquinone’s action on the skin, it can be an irritant, particularly in higher concentrations of 4% or greater and predictably when combined with tretinoin. Some medications have been created that combine 4% hydroquinone with tretinoin and a form of cortisone. The cortisone is included as an anti-inflammatory. The negative side effect of repeated application of cortisone is countered by the positive effect of the tretinoin so that it does not cause thinning of skin and damage to collagen.
Resorcinol or m-hydroquinone is often used in skin-lightener cosmetics in countries where free hydroquinone is prohibited.
Some of alternative lighteners are derived from natural sources of hydroquinone. These include Mitracarpus scaber extract, Uva ursi (bearberry) extract, Morus bombycis (mulberry), Morus alba (white mulberry), and Broussonetia papyrifera (paper mulberry). All of these contain arbutin (technically known as hydroquinone-β-D-glucoside), which can inhibit melanin production. Pure forms of arbutin are considered more potent for affecting skin lightening.
Arbutin is derived from the leaves of bearberry, cranberry, mulberry or blueberry shrubs, and also is present in most types of pears. It can have melanin-inhibiting properties. Arbutin and other plant extracts are considered safe alternatives to commonly used depigmenting agents to make the skin fairer. Medical studies have shown the efficiency of arbutin for skin lightening.There are patents controlling its use for skin lightening. Arbutin actually exists in two isomers, alpha and beta. The alpha isomer offers higher stability over the beta isomer and is the preferred form for skin lightening indications.
Kojic acid is a by-product in the fermentation process of malting rice for use in the manufacturing of sake, the Japanese rice wine. Some research shows kojic acid to be effective for inhibiting melanin production. However, kojic acid is an unstable ingredient in cosmetic formulations. Upon exposure to air or sunlight it can turn brown and lose its efficacy. Many cosmetic companies use kojic dipalmitate as an alternative because it is more stable in formulations. However, there is no research showing kojic dipalmitate to be as effective as kojic acid, although it is a good antioxidant. Further, some controversial research has suggested that kojic acid may have carcinogenic properties in large doses. Other further studies show that kojic acid is not carcinogenic, but can cause allergic contact dermatitis and skin irritation.
Azelaic acid is a component of grains, such as wheat, rye, and barley. It is applied topically in a cream formulation at a 10-20% concentration. Azelaic acid is used to treat acne, but there also is research showing it to be effective for skin discolorations. Other research also indicates azelaic acid may be an option for inhibiting melanin production.
Vitamin C and its various forms (ascorbic acid, magnesium ascorbyl phosphate, etc.) are considered an effective antioxidant for the skin and help to lighten skin. One study found it raises glutathione levels in the body. Another study found that brownish guinea pigs given vitamin C, vitamin E and L-cysteine, simultaneously, led to lighter skin.
Glutathione is a tripeptide molecule found in mammalian bodies. It is an antioxidant that plays an important role in preventing oxidative damage to the skin. In addition to its many recognized biological functions, glutathione has also been associated with skin lightening ability. While skin whitening reduces melanin which serves as the natural protection from UV exposure, glutathione’s antioxidant property also protects the skin from UV radiation.
A double-blind placebo-controlled study found glutathione to be effective as a skin whitening agent and in reducing dark spots; the dose regime was 500 mg per day (split in 2 equal doses per day) for 2 – 4 weeks. In contrast, a study that examined the effect of glutathione and related compounds in-vitro found that glutathione monoethyl ester but not glutathione had a depigmenting effect. A review of the use of glutathione for skin whitening was published in 2016.
Glutathione is an ingredient in some cosmetics preparations. Glutathione for skin whitening is available in cream, soap, lotion, nasal spray and injectable form. Glutathione that is applied on the skin in the form of lotion is not efficiently absorbed by the skin cells as the thiol group undergoes rapid formation of disulfide. When taken orally, glutathione is hydrolyzed by enzymes in the gastrointestinal tract resulting in reduced bioavailability. The level of glutathione increased in smalls amounts temporarily when large oral doses were administered. As a result, the effectiveness of externally administered glutathione is slowed down by its inability to cross cell membranes efficiently and its rapid degradation by enzymes in the gastrointestinal tract. On the contrary, intravenous glutathione delivers very high doses directly into the systemic circulation and is the preferred mode of administering glutathione. However, this method of administrating the antioxidant might flood the cells with glutathione that may cause reductive stress. This might expose people to potential health risks associated with long-term use of high dose of glutathione. Of all the glutathione products, glutathione tablet remains the most effective type.
Glutathione can be combined with many other agents like vitamin C to increase its absorption, N-acetyl cysteine to boost its level, and other antioxidants like vitamin E. Some oral intake of glutathione could have dangerous effect when combined with other skin whitening agents such as hydroquinone which is a carcinogenic element and monobenzone which causes irreversible depigmentation.
Post-melanin synthesis Skin Whitening Agents
Alpha hydroxy acids
Alpha hydroxy acids (AHAs) – primarily in the form of lactic acid and glycolic acid – are the most researched forms of AHAs because they have a molecular size that allows effective penetration into the top layers of skin. It is generally assumed that in and of themselves AHAs in concentrations of 4% to 15% are not effective for inhibiting melanin production and will not lighten skin discolorations in that manner. It is believed that their benefit is in helping cell turnover rates and removing unhealthy or abnormal layers of superficial skin cells (exfoliation) where hyperpigmented cells can accumulate. However, other research has shown that lactic and glycolic acids can indeed inhibit melanin production separate from their actions as an exfoliant on skin.
Alpha hydroxy acid peels (using 50% concentrations or greater) may remove skin discolorations. Only a qualified physician should perform these types of facial peels.
Niacinamide is claimed to be a much safer alternative when applied topically for skin or genitalia whitening. According to research by Procter & Gamble, a cosmetics company, niacinamide has no adverse side-effects. It also promotes acne reduction, increases skin moisture, and reduces fine wrinkles.
Other/ungrouped Skin Whitening Agents
Most commonly, depigmentation of the skin is linked to people born with vitiligo, which produces differing areas of light and dark skin. These individuals, if they so decided to use a lightening process to even out their skin tone, could apply a topical cream containing the organic compound monobenzone to lessen the remaining pigment. Monobenzone may cause destruction of melanocytes and permanent depigmentation. An alternate method of lightening is to use the chemical mequinol over an extended period of time. Increasingly, people who are not afflicted with the vitiligo experiment with lower concentrations of monobenzone creams in the hope of lightening their skin tone evenly. However, monobenzone is not recommended for skin conditions other than vitiligo.
Many skin whiteners contain toxic mercury, such as mercury(II) chloride or ammoniated mercury as the active ingredient. However, mercury has been banned in most countries for use in skin whitening (1976 in Europe, 1990 in the USA) because it accumulates on skin and it can have the opposite results in the long term. As late as January 2016, the FDA published a warning not to use a particular brand of whitener – Viansilk’s “Crema Piel De Seda” (“Silky Skin Cream”), sold in the United States due to its mercury content.
Tranexamic acid is sometimes used in skin whitening as a topical agent, injected into a lesion, and taken by mouth, both alone and as an adjunct to laser therapy; as of 2017 its safety seemed reasonable but its efficacy for this purpose was uncertain because there had been no large scale randomized controlled studies nor long term follow-up studies.
Other options with some amount of research regarding their potential skin lightening abilities are licorice extract (specifically glabridin).
There is also a small amount of research showing oral supplements of pomegranate extract, ellagic acid, vitamin E, and ferulic acid can inhibit melanin production.
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