||This article needs more medical references for verification or relies too heavily on primary sources. (December 2013)|
Skin whitening, skin lightening, and skin bleaching refer to the practice of using chemical substances in an attempt to lighten skin tone or provide an even skin complexion by lessening the concentration of melanin. Several chemicals have been shown to be effective in skin whitening, while some have proven to be toxic or have questionable safety profiles, adding to the controversy surrounding their use and impacts on certain ethnic groups.
- 1 Uses
- 2 Combination treatments
- 2.1 Pre-melanin synthesis
- 2.2 During melanin synthesis
- 2.3 Post-melanin synthesis
- 2.4 Other/ungrouped
- 3 Laser treatments
- 4 Cryosurgery
- 5 Controversy and negative health effects
- 6 See also
- 7 References
Specific zones of abnormally high pigmentation such as moles and birthmarks may be depigmented to match to the surrounding skin. Conversely, in cases of vitiligo, unaffected skin may be lightened to achieve a more uniform appearance.[medical citation needed] Long term use of skin whiteners can lead to pigmentation increasing to the joints of the fingers, toes, buttocks and ears. The skin of the face can become thinned and the area around the eyes can have increased pigmentation causing a 'bleach panda effect'.
2012 sales of skin lightening creams in India alone totaled 258 tons and the global market for skin lighteners is projected to reach US $19.8 billion by 2018 based on sales growth primarily in Asia, Africa and the Middle East.
Most skin-lightening treatments, which can reduce or block some amount of melanin production, are aimed at inhibiting tyrosinase. Many treatments use a combination of topical lotions or gels containing melanin-inhibiting ingredients along with a sunscreen, and a prescription retinoid. Depending on how the skin responds to these treatments, exfoliants — either in the form of topical cosmetic or chemical peels — and lasers may be used. New development using LED systems are also showing good results.
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
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) 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.
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 countries (e.g. France) because of fears of a cancer risk.
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 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. Safer alternatives are more expensive but are available.
Some of alternative lighteners are natural sources of hydroquinone. They 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.[not in citation given] 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.[medical citation needed] 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, lead 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. The role of glutathione as a skin whitening was discovered as a side effect of large doses of glutathione. Glutathione utilizes different mechanisms to exert its action as skin whitening agent at various levels of melanogenesis. It inhibits melanin synthesis by means of stopping L-DOPA’s ability to interact with tyrosinase in the process of melanin production. Research result from a study  shows that glutathione inhibits the actual production as well as agglutination of melanin by interrupting the function of L-DOPA. Another study found that glutathione inhibits melanin formation by direct inactivation of the enzyme tyrosinase by binding and chelating copper within the enzyme’s active site. Glutathione’s antioxidant property allows it to inhibit melanin synthesis by quenching of free radicals and peroxides that contribute to tyrosinase activation and melanin formation. Its antioxidant property also protects the skin from UV radiation and other environmental as well as internal stressors that generate free radicals that cause skin damage and hyper-pigmentation. In most mammals, melanin formation consists of eumelanin (brown-black pigment) and pheomelanin ( yellow-red pigment) as either mixtures or co-polymers. Increase in glutathione level may induce the pigment cell to produce pheomelanin instead of eumelanin pigments. A research by Te-Sheng Chang found lowest levels of reduced glutathione to be associated with eumelanin type pigmentation, whereas the highest ones were associated with the pheomelanin. As a result, it is reasonable to assume that depletion of glutathione would result in eumelanin formation. Prota  observed that decreased glutathione concentration lead to in the conversation of L-dopaqunione to L-dopachrome increasing the formation of brown-black pigment (eumelanin).
Glutathione is a best ingredients in use of cosmetics preparation. 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.
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.
Cinnamomum subavenium, a Chinese herb, has been suggested for use as a skin whitening agent. The plant contains substances which inhibit production of tyrosinase, an enzyme which catalyzes the production of melanin. The herb has not been established as either effective or safe but is being researched by Hui-Min Wang and his colleagues at Kaohsiung Medical University in Taiwan where experiments shown that it was effective at causing Zebrafish to lose their stripes.
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.
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. Some studies suggest that long-term use could cause systemic absorption that leads to tissue accumulation of the substance.
Both ablative and nonablative lasers can have a profound effect on melasma. However, the results are not always consistent, and problems have been reported (such as hypo- or hyperpigmentation). Laser treatments of this kind are more likely to result in problems for those with darker skin tones.
Another alternative to laser treatment is cryosurgery using liquid nitrogen. Controlled destruction of skin cells causes the skin to naturally regenerate itself. Excess melanin comes to the surface and peels off in a few days. This is particularly useful in sensitive areas like the genitals where laser treatment could leave a scar. Efficacy of the treatment depends on the depth of the pigment. Freckles in any part of the body can be treated the same way.
Controversy and negative health effects
There is evidence to suggest that some types of skin-whitening products use active ingredients (such as mercurous chloride) and hydroquinone which can be harmful. Hydroquinone had been banned in Europe. However, it is now available again but only when prescribed by a medical doctor. This is also the case in many other countries, where hydroquinone can only be prescribed by a doctor for certain skin conditions.
There is a growing market in skin lightening products that are toxin-free. However, they are more costly due to their expensive ingredients. Japan and the Pacific are big markets for high quality skin lightening products imported from Europe.
- Anal bleaching
- Colonial mentality
- Venetian Ceruse - white lead based cosmetic worn by Elizabeth I of England.
- Sun tanning
- Racial whitening
- Pale (skin tone)
- Tooth bleaching
- Whiteness in Japanese culture
- Rashid, Aliya (Sep 1, 2006). "A rush to cream the fairness fetish". NDA India.
- Olumide, Y. M. (2010). "Use of skin lightening creams". BMJ 341 (nov23 2): c6102–c6102. doi:10.1136/bmj.c6102. ISSN 0959-8138.
- Narayan, A. Bloomberg Business Week, A Lucrative Promise for India's men: Whiter skin, Dec 5, 2013
- McDougall, A. Cosmeticsdesign-Asia.com, Skin lightening trend in Asia boosts global market.
- Journal of the American Academy of Dermatology: 272–281. 2006.
- Dermatologic Surgery: 365–371. 2006.
- Journal of Drugs in Dermatology: 27–34. 2004.
- International Journal of Dermatology: 966–972. 2003.
- Archives of Dermatology: 1578–1582. December 2002.
- Dermatologic Surgery: 365–371. March 2006.
- Acta Dermato-Venereologica: 305–310. July 1999.
- International Journal of Dermatology: 286–292. April 1998.
- Journal of the American Academy of Dermatology: S27–S36. March 1997.
- Cutis: 177–184. March 2006.
- Journal of Drugs in Dermatology: 592–597. September–October 2005.
- Journal of Cosmetic Science: 208–290. May–June 1998.
- Dermatological Surgery: 443–447. May 1996.
- Journal of Natural Products: 1605–1611. November 2002.
- Journal of Dermatological Science: 68–75. August 2001.
- British Journal of Dermatology: 493–500. March 2003.
- Fuller, Thomas (2006-05-14). "A Vision of Pale Beauty Carries Risks for Asia's Women". The New York Times. Retrieved 2010-05-23.
- Drugs in Dermatology: 377–381. July–August 2004.
- Maeda, K; Fukuda, M (1996). "Arbutin: mechanism of its depigmenting action in human melanocyte culture". Journal of Pharmacology and Experimental Therapeutics 276 (2): 765–769. PMID 8632348.
- Jun, So-Young; Park, Kyung-Min; Choi, Ki-Won; Jang, Min Kyung; Kang, Hwan Yul; Lee, Sang-Hyeon; Park, Kwan-Hwa; Cha, Jaeho (2007). "Inhibitory effects of arbutin-β-glycosides synthesized from enzymatic transglycosylation for melanogenesis". Biotechnology Letters 30 (4): 743–8. doi:10.1007/s10529-007-9605-1. PMID 18040603.
- Archives of Pharmacal Research, August 2001, pages 307-311.
- Mutation Research, Genetic Toxicology and Environmental Mutagenesis, June 2005, pages 133-1450 and Toxicological Sciences, September 2004, pages 43–49.
- Serra-Baldrich, E., Tribô, M. J. and Camarasa, J. G. (1998), Allergic contact dermatitis from kojic acid. Contact Dermatitis, 39: 86–87. doi:10.1111/j.1600-0536.1998.tb05843.x
- "Plastic Surgery Articles (Indications, Anatomy, Workup, Surgical Therapy, Treatment, Complications) - Medscape Reference". Retrieved 29 May 2014.
- Baliña, Luis M.; Graupe, Klaus (December 1991). "The Treatment of Melasma 20% Azelaic Acid versus 4% Hydroquinone Cream". International Journal of Dermatology 30 (12): 893–895. doi:10.1111/j.1365-4362.1991.tb04362.x.
- Rendon, Marta; Berneburg, Mark; Arellano, Ivonne; Picardo, Mauro (May 2006). "Treatment of melasma". Journal of the American Academy of Dermatology. Supplement 2 54 (5): S272–S281. doi:10.1016/j.jaad.2005.12.039.
- Johnston, CS; Meyer, CG; Srilakshmi, JC (1993). "Vitamin C elevates red blood cell glutathione in healthy adults". The American journal of clinical nutrition 58 (1): 103–5. PMID 8317379.
- Fujiwara, Yoko; Sahashi, Yumiko; Aritro, Mitsumi; Hasegawa, Satoko; Akimoto, Koji; Ninomiya, Shinji; Sakaguchi, Yasue; Seyama, Yousuke (2004). "Effect of simultaneous administration of vitamin C, L-cysteine and vitamin E on the melanogenesis". BioFactors 21 (1–4): 415–8. doi:10.1002/biof.552210182. PMID 15630239.
- Jansen, A. H.; Russell, B. J.; Chernick, V (1975). "Respiratory effects of H+ and dinitrophenol injections into the brain stem subarachnoid space of fetal lambs". Canadian journal of physiology and pharmacology 53 (5): 726–33. PMID 134.
- Libíková, H; Pogády, J; Wiedermann, V; Breier, S (1975). "Search for herpetic antibodies in the cerebrospinal fluid in senile dementia and mental retardation". Acta virologica 19 (6): 493–5. PMC 2443094. PMID 1996.
- Prasad, Sahdeo; Srivastava, Smita; Singh, Madhulika; Shukla, Yogeshwer (2009). "Clastogenic Effects of Glyphosate in Bone Marrow Cells of Swiss Albino Mice". Journal of Toxicology 2009: 1. doi:10.1155/2009/308985.
- Matsuki, M; Watanabe, T; Ogasawara, A; Mikami, T; Matsumoto, T (2008). "Inhibitory mechanism of melanin synthesis by glutathione". Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 128 (8): 1203–7. doi:10.1248/yakushi.128.1203. PMID 18670186.
- Scott, D. M.; Mazurkiewicz, M; Leeman, P (1976). "The long-term monitoring of ventilation rhythms of the polychaetous annelid Nereis virens sars". Comparative biochemistry and physiology. A, Comparative physiology 53 (1): 65–8. PMID 187.
- Karg, E; Odh, G; Wittbjer, A; Rosengren, E; Rorsman, H (1993). "Hydrogen peroxide as an inducer of elevated tyrosinase level in melanoma cells". The Journal of investigative dermatology 100 (2 Suppl): 209S–213S. PMID 8433009.
- Shindo, Y; Hashimoto, T (1995). "Antioxidant defence mechanism of the skin against UV irradiation: Study of the role of catalase using acatalasaemia fibroblasts". Archives of dermatological research 287 (8): 747–53. PMID 8554387.
- Ito, S (1993). "High-performance liquid chromatography (HPLC) analysis of eu- and pheomelanin in melanogenesis control". The Journal of investigative dermatology 100 (2 Suppl): 166S–171S. PMID 8433004.
- Jara, J. R.; Aroca, P; Solano, F; Martinez, J. H.; Lozano, J. A. (1988). "The role of sulfhydryl compounds in mammalian melanogenesis: The effect of cysteine and glutathione upon tyrosinase and the intermediates of the pathway". Biochimica et Biophysica Acta 967 (2): 296–303. PMID 2903772.
- Libíková, H; Pogády, J; Wiedermann, V; Breier, S (1975). "Search for herpetic antibodies in the cerebrospinal fluid in senile dementia and mental retardation". Acta virologica 19 (6): 493–5. PMC 2443094. PMID 1996.</pmid>
- Tan, A. W.; Nuttall, F. Q. (1975). "Characteristics of the dephosphorylated form of phosphorylase purified from rat liver and measurement of its activity in crude liver preparations". Biochimica et Biophysica Acta 410 (1): 45–60. PMID 75.
- Antonovski, L; Ljatkova, K; Sukarov, L. L.; Brenner, W. E.; Edelman, D. A.; Bernard, R. P. (1975). "A comparative study of metal and plastic (Karman) cannulae for first trimester abortion by suction curettage". International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 13 (1): 33–8. PMID 259.
- Witschi, A; Reddy, S; Stofer, B; Lauterburg, B. H. (1992). "The systemic availability of oral glutathione". European journal of clinical pharmacology 43 (6): 667–9. doi:10.1007/BF02284971. PMID 1362956.
- Schmoldt, A; Benthe, H. F.; Haberland, G (1975). "Digitoxin metabolism by rat liver microsomes". Biochemical pharmacology 24 (17): 1639–41. doi:10.1016/0006-2952(75)90094-5. PMID 10.
- Järvisalo, J; Saris, N. E. (1975). "Action of propranolol on mitochondrial functions--effects on energized ion fluxes in the presence of valinomycin". Biochemical pharmacology 24 (18): 1701–5. PMID 13.
- Idler, D. R.; Burton, M. P. (1976). "The pronephroi as the site of presumptive interrenal cells in the hagfish Myxine glutinosa L". Comparative biochemistry and physiology. A, Comparative physiology 53 (1): 73–7. PMID 190.
- Bhanoo, Sindya N. (December 15, 2011). "An Herbal Alternative to Creams for Pale Skin". New York Times. Retrieved March 30, 2011.
- Experimental Dermatology, January 2003, supplemental. pages 43-50.
- Dermatologic Surgery, February 2005, pages 149-154; Journal of Cutaneous Medicine and Surgery, April 2004, pages 97-102; Cutis, February 2004, supplemental, pages 18-24; Dermatologic Therapy, June 2004, pages 196-205; and Dermatological Surgery, June 1999, pages 450-454.
- Procter & Gamble. "Skin lightening products" (PDF).
- "Skin lightening products".
- Experimental Dermatology, August 2005, pages 601-608; Bioscience, Biotechnology, and Biochemistry, December 2005, pages 2368-2373; International Journal of Dermatology, August 2004, pages 604-607; Journal of Drugs in Dermatology, July–August 2004, pages 377-381; Facial and Plastic Surgery, February 2004, pages 3-9; Dermatologic Surgery, March 2004, pages 385-388; Journal of Bioscience and Bioengineering, March 2005, pages 272-276; Journal of Biological Chemistry, November 7, 2003, pages 44320-44325; Journal of Agriculture and Food Chemistry, February 2003, pages 1201-1207; International Journal of Cosmetic Science, August 2000, pages 291-303; and Anti-Cancer Research, September–October 1999, pages 3769-3774.
- Journal of the American Academy of Dermatology, May 2006, supplemental, pages 262-271; Dermatologic Therapy, January 2001, page 46; Journal of Cosmetic and Laser Therapy, March 2005, pages 39-43; Journal of Cutaneous Medicine and Surgery, April 2004, pages 97-102; Journal of Drugs in Dermatology, November–December 2005, pages 770-774; Dermatologic Surgery, October 2005, page 1263; and Lasers in Surgery and Medicine, April 2000, pages 376-379.
- Counter, S. Allen, Whitening skin can be deadly, Boston Globe, 16 Dec 2003
- Akortha, E.E.; Niemogha, M.T. and Edobor, O. (1 June 2012). "MUTAGENIC AND GENOTOXIC SCREENING OF EIGHT COMMONLY USED SKIN WHITENING CREAMS IN NIGERIA". Bayero Journal of Pure and Applied Sciences 5 (1): 5–10. doi:10.4314/bajopas.v5i1.2. Retrieved 25 December 2012.
- Global Industry Analysts (GIA) Skin lighteners: a global strategic business report’ 2009