Some quick background on why we pigment: The enzyme Tyrosinase is a catalyst for melanin production. Once this thing starts going, it produces more pigment and sometimes causes the dreaded “dark spots” or discoloration of skin. Many of the most effective ingredients are known as Tyrosinase inhibitors. While tyrosinase inhibitors such as hydroquinone, kojic acid, and arbutin have been shown to be unsafe in some studies, there are plenty of other options for treating hyperpigmentation.
Below is the list of ingredients that have been proven to work in *some* clinical fashion to combat hyperpigmentation whether it’s from PIH (post-inflammatory hyperpigmentation, usually from acne) or Melasma.
Tyrosinase Inhibitors
- Hydroquinone has been the main treatment for PIH because of it’s ability to inhibit tyrosinase and actually decrease the number of melanocytes present. In a study with Fitzpatrick skin types IV–VI (darker skin tones), they found that it was effective for both PIH and Melasma. However, people have reported negative side effects such as dermatitis, nail discoloration, hypopigmentation, and in some cases, worse hyperpigmentation. In 2006, the FDA banned over the counter hydroquinone based on rodent studies suggesting that it may be a carcinogen. PMID: 20725554.
- Retinol: Retinoids are variants of vitamin A, and are generally effective alone or in combination with other treatments for hyperpigmentation. However, 50% of patients in a study with skin of color developed dermatitis (red, itchy, scaly rashes). Starting at lower concentrations and titrating up is recommended for skin of color. PMID: 20725554.
- Arbutin: Extracted from bearberry, pear, cranberry, or blueberry plants. Arbutin causes depigmentation by inhibiting not only tyrosinase activity. However, higher concentrations of arbutin can lead to a paradoxical hyperpigmentation. A clinical study of 3% deoxyarbutin was shown to be effective in the treatment of sun spots in light-skinned patients, but there was no significant clinical response in the subset of dark-skinned patients. PMID: 20725554.
- Azelaic acid: Better tolerated than Retinoids in skin of color. Azelaic acid depigments the skin in two ways: 1) inhibits tyrosinase and 2) blocks DNA synthesis of abnormal melanocytes. People with PIH and melasma can use creams with up to 20% safely. Noticeable differences seen in a study after 24 weeks of use. PMID: 20725554
- Kojic acid: It is able to depigment darker areas by chelating copper (binding to copper ions to reduce activity/transport), and therefore inhibits tyrosinase production. Usually formulated with other ingredients such as glycolic acid and hydroquinone to increase efficacy. Has been shown to help melasma in Caucasian and Asian skin but not yet proven to treat PIH in darker skin. Contact dermatitis is also a common side effect so best to use with caution. PMID: 20725554
- N-acetyl glucosamine (NAG): is an amino sugar that is a precursor to hyaluronic acid. It works by inhibiting tyrosinase glycosylation (molecular processing), a step necessary in the production of melanin. Generally well tolerated. Used in 2% concentrations alone or with niacinamide. Shown to significantly lighten hyperpigmented areas caused by sun exposure in lighter skinned patients. However, more clinical studies are needed to determine the effectiveness in darker skin tones.
- Licorice root extract Licorice. Licorice root extract is anti-inflammatory, antiviral, antimicrobial, and anticarcinogenic properties.Some of the active ingredients in licorice root extract include glabridin, which inhibits tyrosinase and possesses anti-inflammatory effects, and liquiritin, which does not inhibit tyrosinase but causes depigmentation by melanin dispersion and removal.One study conducted in 20 Egyptian women showed that topical liquiritin cream (1g/day) for four weeks was both safe and effective in the treatment of melasma. Side effects were minimal. Further clinical studies with racial/ethnic patients are needed to evaluate the efficacy of licorice root extract in the treatment of PIH. PMID: 20725554.
- Black tea, White tea, and Green Tea are powerful natural tyrosinase inhibitors. They also happen to have strong antioxidant properties which help to prevent free radicals. Black fermented tea in particular decreases tyrosinase levels. In some cases, the effects were superior to Arbutin. PMID: 25643794.
- Tranexamic Acid: The most clinical evidence for tranexamic acid has been with the use of oral tranexamic acid. In Asian skin over 8-12 weeks, studies show that it was able to reduce melasma with mild side effects. Generally it is used in cases that are unresponsive to topical hydroquinone. PMID: 29677015.
Indirect Inhibitors
- Niacinamide. The active form of vitamin B3, or niacin, has shown to significantly decrease melanosome (pigment storage) transfer to keratinocytes (90% of skin cells) without inhibiting tyrosinase activity. Efficacy has not been studied for darker skin however 2-5% in combination with N-acetyl glucosamine (NAG) has shown to be effective for melasma treatment in lighter skin. PMID: 20725554.
- Ascorbic acid aka Vitamin C is an antioxidant derived from fruits and vegetables. AA causes skin lightening by interacting with copper ions at the tyrosinase active site and by blocking melanin synthesis. Can also be anti-inflammatory and photoprotective. Generally used in concentrations of 5-10% to be effective and can be combined with other depigmenting agents such as hydroquinone. Generally well tolerated but most studies involved treatment of melasma rather than PIH. PMID: 20725554.
Exfoliators
- Glycolic acid: found in sugarcane, is a natural occurring AHA (alpha-hydroxy acid) that encourages skin peeling and increases collagen. In a clinical study of 16 darker skinned patients with Fitzpatrick skin types IV to VI, they saw hyperpigmentation reduction after using 2% hydroquinone/tretinoin cream + six glycolic acid peels (at 50-68%) over 22 weeks. PMID: 20725554.
- Salicylic acid (SA): Derived from willow tree bark, is a BHA (beta-hydroxy acid) that is Eepecially effective in acne-induced PIH. The safety and efficacy of SA peels in the treatment of PIH has also been demonstrated in even higher skin phototypes V and VI. PMID: 20725554.
- Lactic acid has proven to be an effective and safe peeling agent in the treatment of melasma with less side effects. PMID: 23248362, 31531176.
Photoprotection
- Sunscreen (SPF 30) provides photo protection Sunscreen (SPF 30). Integral for the treatment of PIH. Daily broad-spectrum sunscreen with a sun protection factor (SPF) of 30 and sun-protective proactive measures can really help to reduce the effects of UV irradiation, which can cause further hyperpigmentation. PMID: 20725554.
