The preference for dark skin vs. light skin has passed in and out of fashion many times in history, but an even colored complexion has always been desired. Women in particular, have sought creams or treatments that would help lighten dark splotches or regions of excess pigmentation (hyperpigmentation), referred to as melasma, freckles, and liver spots. Both men and women have interest in fading age spots, and people with vitiligo, a condition involving areas lacking pigmentation, often use skin lighteners to even out pigmentation.

Melasma occurs in women more frequently than men. It affects all races, but is more common in people with darker complexions. It generally arises in females after puberty and is associated with hormonal changes, especially during pregnancy. The use of birth control pills and hormone replacement therapy are also linked with melasma. The darkened areas may persist after childbirth or with the discontinuation of hormone therapy. Other factors commonly associated with melasma include genetics and exposure to UV light.

The production of pigment within melanocytes is a multi step process. The first step involves the enzyme tyrosinase. Tyrosinase is the preferred drug target at this time because inhibiting this enzyme can block all the pigment producing pathways. Exposure to the sun increases the activity of tyrosinase and results in tanning. However, in certain people it can lead to areas of hyperpigmentation, including melasma, and increases the risk of developing skin cancer.

Hydroquinone
The most common drug used in the US as a skin lightener is hydroquinone (1.5 to 4% commercially, or up to 10% in custom made products.) Low concentrations are found in many cosmetics, while the higher concentrations are prescription drugs. It was proposed to inhibit tyrosinase, but recent studies indicate that it destroys melanocytes. In addition, it appears to be mutagenic (cause changes in genetic material) and can produce skin irritation, nail discoloration, and postinflammatory hyperpigmentation.

Cosmetic formulations containing hydroquinone have been banned in several countries including South Africa . Hydroquinone use by persons living in regions receiving a high degree of sunlight has been associated with the development of ochronosis. This is a chronic skin condition characterized by the appearance of sooty pigmentation commonly affecting the cheeks, forehead, and regions surrounding the eyes. European nations have stopped sales of hydroquinone depigmenting creams because of its mutagenic activity.

Azelaic acid
Preparations containing azelaic acid (15-20%) have been used to treat melasma, however it only has FDA approval for use in the treatment of acne. It appears to have selective skin lightening effects on excessively active melanocytes; there are minimal effects on normally pigmented skin. The action of this drug may result from inhibition of enzymes in the energy producing part of the cell and inhibition of DNA synthesis. Allergic sensitization and/or abnormal reactions to sunlight can occur. Other adverse reactions include itching, redness, scaling, and burning.

Tretinoin
Tretinoin 0.05-0.1% (in RetinAŽ and RenovaŽ ) is a derivative of vitamin A. It is also present and naturally in Rose Hip Oil. The drug is used in the treatment of acne and to decrease the signs of sun damage and normal aging skin, such as fine wrinkles, roughness, and hyperpigmentation. Redness, dryness, and scaling occur frequently, particularly at the beginning of treatment. These reactions may decrease with time, but sometimes requires an adjustment in the dose or discontinuation. Less frequently, contact dermatitis and abnormal pigmentation occur. Rose Hip Oil has all the benefits of tretinoin without the undesired side effects.

Glycolic acid
This alpha hydroxyacid (AHA) is used as a chemical peel to reduce fine wrinkling when applied as a 50-70% solution , but it can reduce pigmentation in the skin after the peeling process subsides. Multiple creams and lotions are available that contain lower concentrations of glycolic acid, often in combination with other skin lightening agents and moisturizers. It is also used in the treatment of acne. Glycolic acid in doses of more than 5% can cause skin irritation, scaling, redness and itching.

Other Cosmetic Ingredients
Arbutin, a hydroquinone derivative isolated from the leaves of the bearberry shrub, has been marketed by a Japanese company as a quasidrug. Magnesium ascorbyl phosphate and niacinamide (nicotinamide) are reported to be active skin lighteners, but solid scientific evidence of their effects are lacking. Some companies are pursuing natural products, such as botanicals containing polyphenols (e.g. green tea extracts). However, in most or all of these cases publications supporting clinical validation of skin lightening claims are not available.