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How to Treat Pigmentation
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Time to read 19 min
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Time to read 19 min
Why do we get pigment spots and skin discolouration? Dr Meder on how to treat common pigmentation concerns safely and effectively.
Melanin is a natural pigment produced by pigment cells called melanocytes in the skin. Melanin defines our skin, hair and eyes colour but the main function of this natural pigment is protective. It protects skin cells and especially DNA information from mutation and all kinds of damage, including free radicals and ultraviolet radiation.
Melanin functions like a solar panel in the skin, but instead of producing energy, it acts as the opposite. It absorbs ultraviolet radiation and converts it to harmless heat radiated on superficial layers of the skin. Also, it is able to interact simultaneously with free radicals transforming them to less active substances unable to damage skin cells. It is one of the most powerful antioxidants and natural UV filters. Alongside with a microbiome, melanin keeps a first line of defence for the skin.
When an amount of melanin is reduced or its production is decreased it makes skin more vulnerable for ultraviolet and air pollution damage. Skin becomes more sensitive and irritated, the barrier function is easily impaired leading to dryness and chronic inflammation. Long story short, we need melanin to maintain skin health.
The amount of melanin in skin is generally controlled by hormonal and oxidative balance in our body. Both male and female hormones, stress hormones and many others can increase the pigment synthesis and make skin darker.
There are many factors influencing skin pigmentation, amongst them inner factors such as inflammation, stress, free radicals and antioxidant activities or external factors such as air pollution, ultraviolet, smoking, heat or cold etc. Inflammation and lack of antioxidants in the skin leads to hyperpigmentation and uneven skin tone. Ultraviolet is the most frequent trigger of hyperpigmentation, sun exposure with lacking or inadequate sun protection causes skin damage and pigmentation troubles.
However, hormonal level, inflammation, stress, skin sensitivity and barrier function all have equally important roles. Hormonal imbalance, chronic inflammation, increased level of stress hormones, higher skin sensitivity and impaired skin barrier are seen as age related changes. Healthy young skin is more resistant to sun damage than mature skin, but in case of sensitization by chemicals, medication, supplements or aggressive skincare young skin could become vulnerable and easily develop different types of dyspigmentation.
Melasma or chloasma. Usually occurring in young females this condition causes irregular dark patches on the face. Melasma can be caused by both sun exposure and female hormonal influences.
Post inflammatory hyperpigmentation (PIH). Hyperpigmentation due to skin inflammation or injury, such as burns, wounds, acne, or skin rashes. The skin looks darker or changes in color after the lesion heals.
Pregnancy mask. Type of melasma developed during a pregnancy due to hormonal changes and sun exposure.
Age spots or solar lentigo. These spots vary from tan to dark brown and are larger than freckles. They develop in adults due to sun exposure or previous sunburns, on areas such as the face, forearms, chest, and tops of the hands.
Age related or maturational pigmentation. Usually affecting the sides of the face, this type of hyperpigmentation refers to gradual darkening of sun-exposed skin in people with darker skin complexions. Hypothetically it is caused by chronic sun exposure and age related metabolic changes.
Periorbital pigmentation located in the eye area. Also referred to as dark circles, this is skin darkening that occurs around the eyes. Most typical for women with Mediterranean or Middle Eastern heritage.
Acanthosis nigricans or pigmentation located in chronically rubbed spots, such as armpits or back of the neck.
Depigmentation resulting from trauma or skin damage when melanocytes are physically destroyed. Chemical and fire burns, infections and massive traumas are amongst the most frequent causes of skin depigmentation. If melanin is destroyed by the immune system it leads to vitiligo, when depigmented white spots appear in different areas of the body. Genetic determination to lack of melanin synthesis manifests as albinism resulting in very pale skin, hair and eyes.
Women tried to eliminate pigmentation for thousands of years as the even and fairer skin tone was seen as a beauty standard since ancient times. The ancient civilisations of China, Egypt and Greece have left us many remedies for skin lightening based on plant extracts or more dangerous substances such as lead, mercury or arsenic. The infamous Venetian ceruse was extremely fashionable in Medieval times causing a lot of poisoning and even deaths amongst aristocrats and rich people of the time. Queen Elisabeth I of England is one of famous victims of this unfortunate trend as her death may have been caused by chronic lead poisoning and the combined use of other dangerous chemicals in her cosmetics, such as mercury and arsenic.
The first deaths linked to use of ceruse for skin lightening were registered in the fifteenth century but people continued to use ceruse for more than three hundred years despite growing evidence of harm and danger. In 1760 ceruse was the cause of death of a London socialite, Maria Coventry, Countess of Coventry. She had been a well known user of ceruse, and is believed to have died of lead poisoning at age 27 as a result of her passion for toxic skincare.
Tragically, toxic and dangerous skin whitening products nowadays are still on sale via Amazon, Ebay, Aliexpress and other online platforms. Multiple research guided by Zero Mercury Working Group regularly finds mercury in skin whitening products sold online.
Research published in 2022 found that almost half of whitening cosmetics samples contained mercury above legal limits. These products are sold in many countries over the world. In Europe and the USA they are most popular amongst women in the African, Indian and Caribbean communities. Despite stereotypes, a significant part of this dangerous product is produced in the USA, UK and EU countries. Use of mercury in skincare is officially forbidden as health hazardous in most countries over the world, including USA, EU and UK.
The use of skincare contaminated by mercury leads to kidney damage, psychosis, depression, development of detrimental neurological conditions and sometimes even to deaths.
Further Readings
→ Melasma, Sun Spots and Post-Inflammatory Pigmentation
→ Why Skin Changes Color and How to Prevent Hyperpigmentation
Plants extracts and exfoliating agents have been traditionally used for skin lightening.
In the 20th century, the new generation of chemically synthesized ingredients able to block melanin synthesis was introduced on the market. Amongst them have been hydroquinone, retinol and its derivatives, hydroxy acids and steroid hormones. All of them are able to efficiently reduce pigmentation but no one is known to be totally safe. One of the safest ingredients is niacinamide while used in high concentrations, but it acts very differently. Niacinamide partially blocks transfer of melanin from pigment cells to the superficial skin layer resulting in lightened skin tone.
Hydroquinone
Retinoic acid/Tretinoin, Retinol, Retinyl aldehyde
Hexylresorcinol
Glycolic acid
Azelaic acid
Kojic acid
Salicylic acid
Topical corticosteroids (fluocinolone and others)
Monobenzyl ether of hydroquinone (MBE) was first discovered as a potential treatment for hypermelanosis in 1939. Several African–American tannery workers experienced localized depigmentation due to their exposure to MBE, a rubber antioxidant found in the gloves of workers. This discovery led to the exploration of MBE as a depigmenting agent. Topical MBE was found to be associated with irritation, sensitization, and a specific form of depigmentation called leukomelanoderma. The depigmenting effects of MBE would sometimes continue to spread even after discontinuing use. These adverse effects made MBE unfit for safe and efficacious treatment of hyperpigmentation.
Hydroquinone, which was called a gold standard for hyperpigmentation treatment, has been in topical use since the 1960s and acts by inhibiting activity of the key enzyme of melanin synthesis tyrosinase. One of the first efficient treatment protocols of melasma was created by Dr. Resnick in the 1960s. At this time, he suggested that the best therapy available for melasma was cessation of oral contraception, decreased exposure to sunlight with use of sunscreens to protect from UV light, and 2%–5% hydroquinone applied to affected areas two times a day. In 1975, Kligman et al. created the triple combination cream combining topical retinoic acid, corticosteroid hormone dexamethasone and hydroquinone for skin lightening. This solution is still in use today despite growing evidence of higher risk of skin damage including irreversible skin conditions such as ochronosis, especially amongst people with darker skin tone.
In 2006, the United States Food and Drug Administration revoked its previous approval of hydroquinone and proposed a ban on all over-the-counter preparations. The FDA officially banned hydroquinone in 2020 as part of a larger reform of the over-the-counter drug review process. The FDA stated that hydroquinone cannot be ruled out as a potential carcinogen. The recent U.S. ban follows prior bans in other parts of the world like Japan, Australia and Europe. Main health concerns related to hydroquinone use are related to its potential harm for skin and health in general as hydroquinone works by decreasing the production and increasing the degradation of melanin pigments in the skin. This increases the skin’s exposure to UVA and UVB rays with growing scientific evidence it can increase the risk of skin cancer. Also, hydroquinone is linked to a skin condition called ochronosis in which the skin thickens and turns bluish-grey. People with darker skin types are at higher risk of developing this condition.
The introduction of laser therapy transfigured the treatment options for many skin disorders, especially hyperpigmentation. The safety and efficacy of lasers remains debatable. However, many hyperpigmentation disorders have been treated with good results using laser therapy. Melanin in the skin can be reduced and evened out by lasering the afflicted area, leading to a more even complexion. As time goes on, technological development means that lasers are more and more efficient.
Intense pulsed light (IPL) has shown promising improvements in the treatment of hyperpigmentation. Due to possible alterations in parameters such as wavelength and fluence, it is frequently used for melanocytic lesions, hair removal, vascular lesions, and melasma.
Another widely used option for hyperpigmentation is Q-Switched neodymium-doped yttrium aluminium garnet (QS Nd:YAG) laser. This laser is highly selective, having a longer wavelength and hence does not damage the epidermis but is very well absorbed by melanin cells at low doses. Pulsed-dye laser or PDL is believed to reduce melanocyte stimulation by targeting the vascular components in lesions. Furthermore, Q-switched ruby laser or QSRL has been widely studied for hyperpigmentation but its efficacy remains questionable although its mechanism is similar to QS Nd:YAG laser. Since the QSRL has a wavelength of 694 nm, it was thought to be highly selective toward melanosomes compared with QS Nd:YAG laser with a wavelength of 1,064 nm. The erbium:YAG is a laser having wavelength of 2,940 nm which ablates skin with least thermal damage and thus, reduces the risk of post-inflammatory hyperpigmentation.
Unfortunately, side effects such as post-inflammatory pigmentation (PIH) and relapses after laser or IPL treatments are frequent leading to low level of patients satisfaction.
Among many existing pigmentation treatments, 4% hydroquinone topical formulations was a gold standard, but US-FDA banned overall OTC preparations of hydroquinone in 2006 following bans of hydroquinone in Japan, Australia and EU due to its potential carcinogenicity and skin damage.
After the ban, many topical drugs such as azelaic acid, tretinoin, and kojic acid have entered the market. Although these drugs are effective, they have long treatment durations, poor penetration, and poor pigment cells targeting. Later, chemical peels were employed as they cause the complete removal of the damaged skin, allowing regeneration of the skin cells. Yet, they have a risk of inflammation, scarring and changes in natural skin color especially in people with darker skin types.
A wide variety of lasers too can be employed in the treatment of hyperpigmentation along with drugs; however, the safety aspect of using lasers remains questionable. Considering all the conventional therapies, there is an underlying need for safe, more evolved therapeutics for hyperpigmentation.
As you can see, most of the ingredients traditionally used for skin lightening are more or less harmful for skin. New generation of lightening ingredients is less focused on active destruction of melanin but using advanced technology and highly efficient targeting for new compounds, interacting on different steps of pigmentation pathways. Smart molecules, receptors-selective and neuromodulatory ingredients such as peptides alongside prebiotics and probiotics, plant extracts and antioxidants are used nowadays to create highly efficient but safe and inclusive products to reveal a natural skin color and improve skin’s overall resilience.
Cysteamine is a derivative of amino acid cysteine, circulating in the human body and known to be a potent antioxidant able to protect cells against mutations caused by different types of radiation. Cysteamine acts as a topical skin lightening agent through several mechanisms.
The inhibition of key melanogenic enzymes. Cysteamine inhibits tyrosinase and peroxidase, which are essential enzymes in the melanin production pathway. By blocking these enzymes, cysteamine reduces melanin synthesis in melanocytes.
Antioxidant activity. Cysteamine exhibits antioxidant properties, helping to neutralize reactive oxygen species (ROS) in the skin. This is important because UV radiation and other external factors can stimulate melanin production by increasing ROS levels in skin cells.
Interference with melanin synthesis pathways. Cysteamine is a metabolite of L-cysteine and affects the anabolic and catabolic pathways of cysteine and glutathione, which are involved in melanogenesis. By altering these pathways, cysteamine can reduce overall melanin production.
Possible effects on melanosomes. Some research suggests that cysteamine may interfere with melanosome formation or transfer, though this mechanism is less well-established.
The reduction of oxidative stress. By decreasing oxidative stress in skin cells, cysteamine may indirectly reduce melanin production, as oxidative stress is known to stimulate melanogenesis.
It's worth noting that cysteamine's efficacy as a skin lightening agent has been demonstrated in several clinical trials, with some studies showing comparable or even superior results to traditional treatments like hydroquinone. Additionally, cysteamine appears to have a favorable safety profile compared to some other skin lightening agents, making it an increasingly popular option for treating hyperpigmentation disorders.
A derivative of another natural amino acid lysine originally designed to prevent and treat excessive bleeding. Topical tranexamic acid acts as a skin lightening agent interacting with various pathways of melanin formation.
The inhibition of melanin synthesis. Tranexamic acid inhibits tyrosinase activity, which is a key enzyme in melanin production. This directly reduces melanin synthesis in melanocytes.
Interference with melanocyte-keratinocyte interaction. It alters the interaction between melanocytes and keratinocytes, which is important for melanin transfer and distribution in the skin.
The reduction of vascular components. Tranexamic acid causes shrinkage of dermal blood vessels. This is significant because increased vascularity can contribute to hyperpigmentation, especially in conditions like melasma.
Anti-inflammatory effect. It provides a specific anti-inflammatory action, which can help reduce pigmentation caused by inflammation.
Plasminogen inhibition. Tranexamic acid inhibits the conversion of plasminogen to plasmin. Plasmin is involved in various processes that can increase melanin production, so inhibiting this pathway helps reduce pigmentation.
Modulation of blood flow. It affects blood flow through interactions with VEGF-1 and plasminogen receptors that interact with melanocytes.
Skin barrier restoration. Tranexamic acid helps calm the skin and restore the skin barrier, which can indirectly contribute to reducing pigmentation.
When applied topically, tranexamic acid penetrates the skin to exert these effects. It's particularly effective for superficial melasma treatment and has shown promising results in clinical studies.
Different types of peptides have been recently designed for skin topical lightening. Peptides act as messengers or signal molecules able to intervene in various stages of melanin formation, maturation or transfer to skin cells.
Melanostatine is a biomimetic peptide which inhibits the synthesis of melanin induced by hormone α-MSH and prevents its hyperproduction for better control over skin tone and age spots. Melanostatine does not interfere with the melanocyte’s functions thus it is an ideal skin-lightening agent for cosmetic products that inhibits melanogenesis without cytotoxicity.
ß-White™ reduces melanin synthesis and tyrosinase activity. Melanin synthesis is an enzymatic process that transforms tyrosine into eumelanin (a brownish-black pigment) and pheomelanin (reddish-brown pigment). The unique inhibitory effect of MITF (= Microphthalmia-associated process transcription factor) sets it apart from traditional skin-lightening components.
White Pure X-50 Peptide is an innovative delivery system that combines two peptides in the same particle turning it into a “smart capsule” which is able to identify and target itself specifically to melanocytes controlling tyrosinase expression but not its activity. This intelligent system is a dual layer capsule that anchors peptides on its surface to create an ITD (Intelligent Target Device) also known as cosmetic drone and focuses only on the areas in which melanin is over-expressed and does not affect surrounding non-melanogenic cells. It reveals a natural and most even skin tone possible without any hint of the halo effect caused by traditional skin lighteners. The ability to target melanocytes specifically, gradually releasing peptides makes this innovative ingredient truly unique. White Pure X50 inhibits the formation of melanin and efficiently controls and prevents UV and non-UV induced hyperpigmentation.
Geno-White peptide is an inhibitor of melanogenic cytokines (SCF & ET-1) able to suppress melanin synthesis but also formation and transfer of melanosomes. This ability helps to prevent an air-pollution caused pigmentation as well as sun-induced.
Tetrapeptide-30 is a skin-brightening peptide consisting of four amino acids acting as a tyrosinase inhibitor, lightening hyperpigmentation and evening out skin tone by reducing the amount of tyrosinase and inhibiting melanocyte activation.
Recent studies showed some probiotic strains, including Bacillus subtilis, Lactobacillus helveticus, Leuconostoc mesenteroides, Bifidobacterium, Lactobacillus plantarum, Pediococcus acidilactici, demonstrate efficacy in skin-lightening through inhibiting melanin synthesis. The cell membranes of some of these beneficial microorganisms contain substances such as lipoteichoic acid able to control pigmentation and reduce melanin synthesis.
Prebiotics are used in skincare formulations to promote the growth of skin lightening microbiome and to suppress inflammatory bacteria such as C.acnes.
Prebiotics Bioecolia (alpha-oligosaccharide), Inulin, Yacon extract and others are well known for their ability to calm down skin inflammation and recently they became a part of brightening skin’s formulations.
Symbiotic complexes including probiotics and prebiotics are new cosmetic trends in sensitive and anti-aging skincare, but also in skin brightening and lightening formulations.
The best known natural ingredients with lightening effect are licorice extract and bearberry extracts.
Licorice Extract contains several active compounds that contribute to its skin lightening effects.
Glabridin. This is the main active compound responsible for skin lightening. It inhibits tyrosinase, the key enzyme in melanin production, thereby reducing melanin synthesis in melanocytes.
Liquiritin. This compound helps break down and disperse existing excess melanin in the skin, reducing pigmentation.
Licochalcone A. While not directly involved in lightning, it helps control oil production and protects the skin from sun damage, which can indirectly contribute to a more even skin tone.
Glycyrrhizin. This compound has anti-inflammatory properties that can help reduce skin irritation and redness, contributing to a more even complexion.
Licorice extract is demonstrably effective in treating various hyperpigmentation issues, including melasma, dark spots, and sun damage. Studies have demonstrated that even low concentrations of licorice extract cream can be effective in lightening the skin.
Bearberry extract, also known as Arctostaphylos uva-ursi extract, contains a compound called arbutin, known as a natural derivative of hydroquinone. It works by inhibiting tyrosinase activity, similar to glabridin in licorice extract. This reduces melanin production in the skin.
Bearberry extract also contains antioxidants that can help protect the skin from free radical damage, which can contribute to uneven skin tone and hyperpigmentation.
Both licorice and bearberry extracts are considered gentler alternatives to more aggressive skin lightening agents like hydroquinone. They are suitable for various skin types, including sensitive skin, and can be used in combination with other skincare ingredients to enhance their effectiveness.
Reseda luteola, Aloe vera leaf juice and Parsley extract are also known for their lightening properties same as many other plants containing different antioxidants which help reduce oxidative skin damage and lighten skin.
Ultraviolet radiation causes the excessive formation of free radicals in the skin triggering melanin synthesis and skin darkening. Antioxidant skincare reduces free radicals damage preventing hyperpigmentation and helping to reduce existing dark spots and even skin color. Niacinamide, vitamin C and vitamin E, glutathione and various plant’s extracts are used in skincare formulations aiming at skin pigmentation. Green tea, mulberry, raspberry and blueberry extracts, licorice extract, various citrus fruits extracts, and wakame seaweed extract are amongst the most popular antioxidant substances used to brighten skin.
Mulberry extract. Rich in flavonoids, mulberry extract has been shown to inhibit melanin production and have antioxidant properties.
Niacinamide. A form of vitamin B3, niacinamide has been demonstrated to have skin lightening effects by inhibiting melanosome transfer.
Hesperidin. A flavonoid found in citrus fruits, hesperidin has shown potential in reducing melanin production.
Gentisic acid. Derived from gentian roots, this compound has been studied for its ability to inhibit tyrosinase.
Polyphenols. Found in various plant sources, including green tea and grape seed extract, polyphenols have antioxidant properties and can help reduce hyperpigmentation.
Fucoidan and Laminarin. These polysaccharides, derived from seaweeds, have shown potential in anti-photoaging and skin lightening applications due to their antioxidant properties and ability to protect against UV radiation.
Melanin synthesis pathway is a complex and multistep process where various factors are involved.
Meder’s newest Lumino-Derm skin brightening collection launched in 2024 includes two products for active pigmentation treatment and following maintenance and prevention of unwanted pigmentation. We use several innovative ingredients together to act upon different steps of the pathway for achieving synergistic effects in skin natural brightening.
This unique brightening cream effectively targets excessive pigmentation without causing any skin damage. The first ever brightening cream based on biotechnology, Lumino-Derm calms skin whilst increasing its resilience to UV damage. The formula works for all skin types, ensuring a natural skin tone, even and luminous without the halo effect. The cream does not increase skin sensitivity. Hypoallergenic and safe for all skin types, Lumino-Derm cream is safe during pregnancy and breastfeeding.
Lumino-Derm formula is a powerful combination of natural amino acid cysteamine, anti-inflammatory tranexamic acid, prebiotics and probiotics, organic licorice extract and a groundbreaking peptide X50.
For best results we recommend using Lumino-Derm cream twice a day as a regular moisturizer for at least 8 weeks or longer.
Designed to reveal a natural skin color this unique brightening cream demonstrates a multi-faceted approach to skin lightening.
The inhibition of melanin production through multiple pathways including anti-inflammatory (tranexamic acid), reduction of hormonal stimuli (cysteamine) and antioxidant (licorice extract).
White Pure X50 peptide inhibits the formation of melanin and efficiently controls and prevents UV and non-UV induced hyperpigmentation.
Dispersion of existing melanin in hyperpigmented areas.
The reduction of inflammation and vascular components of pigmentation, including PIH (post inflammatory hyperpigmentation).
Antioxidant protection and prevention of sun-induced skin damage.
The restoration of healthy microbiome, able to prevent and reduce skin hyperpigmentation and maintain overall skin health support.
Lumino-Derm is a revolutionary brightening sheet mask with potent brightening and anti-inflammatory ingredients designed to prevent skin pigmentation including pregnancy mask and sun-induced skin damage.
Hypoallergenic and suitable for all skin types, Lumino-Derm sheet mask is safe to use during pregnancy and breastfeeding when women often experience higher risk of pigmentation. Highly effective mask is also gentle to your skin and doesn't increase sun sensitivity, so you won't need to up your SPF.
For best results we recommend to use it once a week following a gentle skin exfoliation.
The powerful formula includes biotechnological and organic ingredients.
Arbutin. A natural derivative of hydroquinone, arbutin inhibits tyrosinase activity, reducing and controlling melanin production in melanocytes.
Gluconolactone. This polyhydroxy acid (PHA) provides gentle exfoliation, which can help remove dead skin cells containing excess melanin. It also has antioxidant properties that can protect against UV-induced pigmentation.
Peptide Melanostatine. inhibits the synthesis of melanin induced by hormonal stimuli and prevents its over production.
Resveratrol. This potent antioxidant has been shown to inhibit tyrosinase activity and reduce melanin content in melanocytes. It also offers protection against UV-induced damage, which can lead to hyperpigmentation.
Living probiotic bacteria culture derived from Greek yoghurt restores and maintains healthy antioxidant skin microbiome. Probiotics reduce inflammation and strengthen the skin barrier, which contribute to a more even skin tone and enhance the efficacy of the other active ingredients.
Hyaluronic acid. While not a lightening agent itself, hyaluronic acid provides intense hydration helping re-create a healthy environment for skin cell turnover and can enhance the penetration of other active ingredients.
For best results we recommend to use Energy-Net Cleansing Mask and Energy-Soin Antioxidant Serum accompanying Lumino-Derm brightening cream.
Gentle microbiome friendly cleansing mask is enriched with niacinamide and probiotics, helping to reduce pigmentation and control melanin synthesis on a daily basis.
Multi-awarded antioxidant serum was named the Best Niacinamide Skincare and Best Therapy Serum for its ability to transform skin reducing enlarged pores and dark spots, restoring smooth and healthy skin texture.
Once a week we recommend exfoliating skin with our gentle probiotic enzyme exfoliator Enzy-Peel. Unlike traditional fruit acid-based exfoliators, our probiotic enzyme exfoliation is selective, targeting only dead skin cells. This unique approach eliminates the risk of irritation or sensitivity, making it suitable even for sensitive skin. Harnessing the natural exfoliating properties of micronized opal particles, Enzy-Peel Mask deeply cleanses the skin, leaving it incredibly smooth, soft, and glowing.