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Deep Guide to Hyperpigmentation - What causes it and how best to treat it

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This writeup was lead-authored by our senior technical adviser, Sunbin Song, PhD. Sunbin graduated from MIT with a degree in Biology before receiving a doctorate in neuroscience from Georgetown and becoming a research scientist at the NIH. She loves to explore how we can best nurture our body, mind and spirit to live more joyful lives. [Sunbin on Google Scholar / on ResearchGate]


Hi! Welcome to Maelove’s “More than Skin Deep” series. This article presents a different take from our prior newsletters that focused on single ingredient and now offers practical advice on how you can tackle common skin complaints with Maelove products while also educating you on the ingredients and how they work.

In this newsletter, we focus on hyperpigmentation – what causes it and how you can treat it with Maelove products. 

First, some terms to get to know:

  • Epidermis = what we commonly think of as “skin” The very top layer of Epidermis is stratum corneum - the visible skin surface that’s made up of dead keratinocytes.
  • Keratinocytes = makes up the overwhelming majority of cells in epidermis.
  • Melanocytes = rare (about 1% of epidermis) but important cells in epidermis. Melanocytes make melanin.
  • Melanin = pigments that give our skin its color.
  • Dermis = is the layer below epidermis. This is the deep layer where the hair and oil glands are rooted.
  • Macrophages = specialized cells that are part of our immune system. Attack and kill harmful bacteria that cause infection.

epidermis and dermis

How do we get our skin color?

Regardless of skin color, people generally have about the same number of melanocytes (per given unit of body mass) which make up about 1% of epidermal cells.

Melanocytes create melanin, which then gets passed around to neighboring keratinocytes.

There are different types of melanin. There is pheomelanin, which has a yellow to reddish color. And then there are two forms of eumelanins, both of which range in hue from brown to black. Our skin color is determined by the particular mix of melanins produced by our melanocytes.


What does melanin do?

Melanin is our skin’s key protection and healing mechanism.

Melanin serves two crucial functions. First, it directly protects our skin from sun damage by absorbing UV radiation. Think of melanin as our body’s natural chemical sunscreen.

Second, melanin acts as an antioxidant that can scavenge and neutralize reactive oxygen species (ROS). UV radiation generates ROS which are like bullets wreaking havoc on skin microstructure and accelerating aging.

Additionally, melanin can function as an anti-inflammatory. And when our skin is under attack (e.g. a bacterial attack like acne), melanocytes near the wound will pump out more melanin as a defense mechanism. This can result in the hyperpigmentation that is left over from your blemishes. More on this later.


Sounds great! But then, what’s the deal with hyperpigmentation? Why does it occur?

Basically, it goes like: Hyperactive melanocytes -> hyperpigmentation.

When some melanocytes pump out more melanin than other melanocytes, this will lead to hyperpigmented spots and an uneven skin tone.

When combined with inflammation, excess melanin can get lodged in the deeper layers (dermis) of the skin and lead to stubborn hyperpigmentation that’s harder to fade.


What are the specific causes/mechanisms that give rise to hyperpigmentation?

There are 3 main causes of hyperpigmentation: skin injuries (inflammation), sun exposure (UV radiation), and major fluctuations in hormone levels (melasma).

1) Skin injuries and resulting inflammation

A common cause of hyperpigmentation is inflammation after a skin injury (post-inflammatory hyperpigmentation- also known as PIH).

The main causes of PIH include acne lesions, ingrown hairs, abrasions, insect bites, eczema, and contact dermatitis. As you can imagine, damage from UV exposure also leads to inflammation in skin.

Technically speaking:
Inflammation can directly stimulate melanocytes via inflammatory mediators that include prostanoids, cytokines, chemokines, as well as ROS that can be released by inflammatory cells. As part of the immune response, white blood cells will also release leukotrienes (inflammatory chemicals) such as LT-C4 and LT-D4, prostaglandins E2 and D2, thromboxane-2, interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-a, epidermal growth factor, and nitric oxide, all of which have been shown by multiple studies to stimulate melanocytes (Davis and Callender 2010). Finally, damage to epidermal cells will also lead to the release of alpha-melanocyte stimulating hormone (Ortonne and Bissett 2008).

PIH is a more common problem in those with darker skin. A 2002 study showed that amongst peoples of color with acne, 65.3% of African Americans, 52.7% of Hispanics and 47.4% of Asians had acne-induced PIH.

PIH is less common in Asians with lighter skin compared to those with darker skin, and studies show multiple-fold lower prevalence of PIH in lighter versus darker skin types across many races suggesting that the degree of pigmentation of skin is a main factor for PIH development (Davis and Callender 2010, Vashi and Kundu 2013, Woolery-Lloyd and Kammer 2011; figure from Davis and Callender 2010).

acne induced post inflammation hyperpigmentation (PIH)

When hyperpigmentation can become extra-stubborn: While epidermal hyperpigmentation can fade over time, unfortunately, there is a chance that hyperpigmentation from PIH can be particularly long-lasting as melanin can lodge in the dermis layer deep inside the skin. This is because inflammation is part of an immune response.

For example, when bacteria grows inside of a clogged pore, inflammation attracts melanin and other immune cells including macrophages that help fight the bacterial infection. Though macrophages primarily swallow and kill bacteria, they can also inadvertently swallow up melanin.

Now called melanophages due to their coloring, they can lodge in the dermis and give a blue-gray appearance to the skin- much like ink lodged in the dermis can give coloring.

Unlike the epidermis which turns over on a regular basis (more frequently in younger skin), the dermis does not renew. This is why a summer tan will fade over a matter of weeks, while ink for tattoos lodged in the dermis (using a needle for penetration) is relatively permanent. In the same way, dermal melanin may be relatively permanent though it fades over a long time - much like tattoos.

To recap: Skin injury -> more melanin to heal the wound -> can become hyperpigmentation

Reducing inflammation prevents hyperpigmentation: PIH can be thought of as an unwanted side effect of an overactive inflammatory immune response (in a form of melanin over-production).

So, those with PIH should aim to both clear up the source of the skin injury (acne, ingrown hairs etc.) and reduce inflammation to help prevent both easier-to-treat epidermal and harder-to-treat dermal hyperpigmentation.


2) UV and free radical damage are typical culprits

The next common cause of hyperpigmentation is UV damage.

We all know we can tan by sitting in the sun. This is because UV exposure upregulates a-melanocyte stimulating hormone (aMSH), which then stimulates more melanin production (Cui et al. 2007). So far so good right?

Side note: There is a real chemical/biological reason behind why we’re drawn to sunbathing. aMSH is secreted by the keratinocytes from cleavage of pro-opiomelanocortin (POMC) which also releases beta-endorphin- which is why tanning feels so good!

Unfortunately, chronic UV exposure and the resulting free radicals (ROS) wreak general havoc on the skin. This form of chronic skin injury eventually leads to prematurely aged skin (photoaged), with blotchy patches of discoloration called solar lentigines (known commonly as liver spots). In part, solar lentigines are characterized by an uneven proliferation of melanocytes, leading to uneven epidermal hyperpigmentation.

However, like PIH, chronic inflammation from UV injury can also recruit immune cells. This can lead to a build-up of dermal melanophages in solar lentigines and dermal hyperpigmentation (Ortonne and Bissett 2008). Hence, solar lentigines are associated with abnormal melanocyte numbers in the epidermis, as well as dermal hyperpigmentation. Though solar lentigines are mostly benign, persistent chronic UV exposure may eventually lead to skin cancer.

To recap: Chronic UV exposure -> repeating injuries to the skin -> liver spots -> extremely persistent sun exposure can result in “deep” dermal hyperpigmentation that’s very hard to fade.

UV exposure and resultant photoaging and solar lentigines is more common in those with fairer skin types, as the extra melanin in darker skin offers greater protection against UV radiation. In fact, compared to fairer skin, darker skin has up to 70-fold greater protection against skin cancer (Brenner and Hearing 2008).

To repeat the obvious, if you want healthy skin that continues to look great as you age, limit sun exposure and wear sunscreen. Additionally, antioxidants (such as Vitamin C) can help fight free radical damage and help prevent skin injury from UV exposure (which can in turn help prevent hyperpigmentation).


3) Melasma, hormonally influenced hyperpigmentation

Melasma is characterized by acquired hyperpigmentation and has a genetic component. While it mainly affects women, it can also affect men. It is most common in women of Asian, African or Hispanic descent (Wang et al. 2019).

Melasma is characterized by hyperactive melanocytes, and is exacerbated by hormones and UV exposure. Hyperactive melanocytes lead to hyperpigmented spots, which typically align with regions that have the most UV exposure- such as cheeks, forehead, nose, and supralabial regions.

Pregnancy and oral contraceptives can also increase hyperpigmentation, as melanocytes have estrogen receptors and respond to increased estrogen by increasing melanin production.

Thankfully, hyperpigmented spots in melasma tend to be mostly of epidermal origin (shallow) rather than dermal origin (deep). In three separate melasma studies, it was found that melanin in the epidermis increased in hyperpigmented areas by between 35 to 83%, but few dermal melanosomes were identified (Kang and Ortonne 2010).

However, to the extent that hormonal levels from menstrual periods (melasma worsens during the luteal phase when estrogen and progesterone are high) or a baseline level of UV exposure (even with sunscreen) are unavoidable, everyday occurrences, hyperactive melanocytes and resultant hyperpigmentation from melasma may be a chronic and long-term condition. Hence, any short-term solution may only be useful temporarily. Instead, a constant and long-term suppression of hyperactive melanocytes is necessitated for long-term benefits.

While melasma is characterized by hyperactive melanocytes (like PIH and solar lentigines), melasma is a complex condition that is distinguished by other abnormalities as well. First, elastin irregularities in UV exposed spots are more prominent in melasma suggesting greater sensitivity to UV exposure. Next, melasma is also associated with vascular abnormalities like telangiectatic erythema (spider veins), and increased vascularization in regions that are hyperpigmented. Targeting vascular abnormalities can improve hyperpigmentation, thus suggesting a connection between vascular changes and hyperpigmentation (Kang and Ortonne. 2010).

While melasma is still incompletely understood, the good news is that epidermal hyperpigmentation is easier to treat than dermal hyperpigmentation. Using “lightening agents” (more on this in the next section) that suppress melanin production in hyperactive melanocytes, and with epidermal turnover of hyperpigmented spots, hyperpigmentation in melasma responds well to treatment if treatment is used consistently and long-term.


Other possible (and less common) causes

Less common causes of hyperpigmentation are related to dietary deficiencies- in particular, B12 vitamin deficiency. This type of hyperpigmentation can affect hair, skin, and nails, but is reversible with Vitamin B12 supplementation (Baker et al. 1963). Folic acid deficiency, some skin cancers, and other autoimmune and infectious conditions are other rare causes of hyperpigmentation (Desai and Alexis 2014). Zinc deficiency has also been associated with melasma (Mogaddam et al. 2018). Oral supplementation with zinc has been suggested, while topical treatment with zinc however has been tested in melasma and found to be relatively ineffective (Yousefi et al. 2014).

Birthmarks such as Becker’s nevus and cafe au lait macules as well as skin conditions like Nevus of Ota, nevocellular nevi are some other causes (Arora et al. 2012). Rare skin conditions such as acanthosis nigricans can also occur due to genetics, drug side effects, autoimmune diseases, obesity, and diabetes. In some individuals, minor injuries and adverse effects to treatment regimens and infections also lead to hyperpigmentation (Ruiz-Maldonado and Orozco-Covarrubias 1997).


Okay, so what are the treatment options?

The old way - Hydroquinone, the most famous “depigmenting” agent

Let’s go over hydroquinone first. It is the most famous and most often prescribed depigmenting (or "lightening") agent.

Side note: Depigmenting agents function by restricting melanogenesis (the pigmentation pathway by which cells generate melanin) and help the affected site to heal hyperpigmentation. Sometimes the term “lightening” is used in place of “depigmenting.”

As we mentioned above, melanin is great for your skin! Melanin protects your skin from premature aging and skin cancer, so we think it’s unwise to try to lighten skin tone (in fact, even a spray-tan provides sun protection to your skin). The aim rather, is for a more uniform skin tone when using “depigmenting agents” to temper overactive melanocytes and reduce excess melanin production in the hyperpigmented spots.

Depigmenting agents slow down melanin production in melanocytes. Typically, they do so by inhibiting tyrosinase which is an enzyme necessary for melanin production. For this reason, depigmenting agents are often described as tyrosinase inhibitors. Hydroquinone as a standalone ingredient is considered the most effective and the gold standard for tyrosinase inhibitors.

However, there are serious downsides to hydroquinone. This includes skin irritation, contact dermatitis, and a halo of hypopigmentation from skin bleaching. And even more serious, is a permanent blue-black skin discoloration condition called exogenous ochronosis that can occur with long-term use of hydroquinone.

For these reasons, hydroquinone is not suggested for long-term treatment (Zhu and Gao 2008). Due to this serious side effect, as well as hydroquinone’s cytotoxicity to melanocytes, it is banned as a cosmetic ingredient in Europe and Japan- and was even considered for ban by the FDA in 2006 (Davis and Callender 2010). In 2020, an update in the CARES act effectively banned hydroquinone in OTC products in the US.

While still available with a prescription, the Cosmetic Ingredient Review (CIR) committee deems hydroquinone unsafe. Under prescription, dermatologists generally will not recommend long-term usage of hydroquinone due to the risk of exogenous ochronosis.

To recap: due to the number of harmful side effects, hydroquinone is used only for short-term treatment while under a doctor’s supervision. Therefore, hydroquinone is not a long term solution for hyperpigmentation.


Current Method: Combination therapy- Hydroquinone, Tretinoin, Corticosteroid

Let’s quickly recap the causes of hyperpigmentation and uneven complexion:

  • Inflammation (which stimulates melanocytes to produce more melanin in inflamed regions of the skin).
  • UV exposure (which in addition to stimulating melanocytes, can eventually lead to solar lentigines with abnormal proliferation of melanocytes).
  • Melasma (which is characterized by overactive melanocytes in sun exposed regions of the skin).

These causes also can be interrelated (UV exposure creates skin injury and inflammation, and worsens hyperpigmentation in melasma).

In most people, a combination of these interrelated factors lead to hyperpigmentation. This is why COMBINATION THERAPY (using multiple treatments simultaneously) is found to be the most effective treatment. Combination therapies can include depigmenting agents, anti-inflammatories, anti-oxidants, and exfoliants.

Today, when prescribed by a dermatologist, hydroquinone is typically not prescribed alone but rather in a combination therapy form marketed under the name “Triluma.” Triluma contains hydroquinone, tretinoin, and corticosteroid fluocinolone acetonide. This combination approach has been scientifically proven to be more effective than hydroquinone alone in treating PIH, solar lentigines, and melasma (Desai and Alexis 2014).

This combination approach to hyperpigmentation was first pioneered by a dermatologist named Albert Kligman, and for this reason, this type of combination therapy is termed the “Kligman formula.” Basically, it combines a hydroquinone with a retinoid (like tretinoin) and an anti-inflammatory (usually a corticosteroid). (Woolery-Lloyd and Kammer 2011).

The addition of a retinoid to the lightening agent hydroquinone has multiple purposes. First, it can treat the acne that may lead to PIH. Second, retinoids themselves can inhibit the synthesis of tyrosinase, as well as inhibit the transfer of melanin from melanocytes to keratinocytes (which can lead to “lightening” of skin). Third, it can stimulate epidermal turnover, which in turn can help fade existing hyperpigmentation.

However, there are some major downsides to this Klingman formula as well.

Hydroquinone and tretinoin each individually are highly irritating, and in combination, can be so irritating that it causes inflammation severe enough to cause PIH. For this reason, a potent anti-inflammatory in the form of a corticosteroid is added to the formula to prevent inflammation and PIH.

Although corticosteroids can prevent PIH with anti-inflammatory action, it too has side effects. These side effects include irritation and burning sensations, unsightly spider veins, and ironically, may also cause hyperpigmentation (Ruiz-Maldonado and Orozco-Covarrubias 1997).

More effective than hydroquinone alone, this combination approach (lightening agent + retinoid + anti-inflammatory) is considered a current gold standard in hyperpigmentation treatment. However, it also is not considered a long-term treatment, due to cytotoxicity of hydroquinone and the risk of irreversible exogenous ochronosis- which is a permanent blue-black skin condition.

Furthermore, tretinoin is known to be highly irritating and is not recommended for pregnant women, while corticosteroids, though potent anti-inflammatories, are also associated with a host of unwanted side effects.

It could very well be the case here that the cure is worse than the disease.


The Maelove way of treating hyperpigmentation: Hyper-combination approach

While highly effective, the Kligman formula approach is known to be toxic, highly irritating to the skin, and can potentially cause long-term with irreversible side-effects (such as ochronosis).

So we asked ourselves- is it possible to create an effective treatment for hyperpigmentation that is non-toxic, safe for long-term use, while also being soothing and gentle enough for sensitive skin?

We decided the answer was yes! To do so, we relied on a hyper-combination approach in which multiple non-toxic, safe, gentle ingredients with weaker effectiveness, when used together, can be more effective than a single strong ingredient with major side effects. Think of it as a combination approach within a combination approach.

Step 1: using multiple agents to replace hydroquinone

Introducing our new Fade Away serum, our first hyperpigmentation fighting specialist. In creating Fade Away, we replaced depigmenting agent hydroquinone with a trio of natural ingredients that are known to be non-toxic, safe long-term, and gentle on the skin. This trio of hyperpigmentation fighters – arbutin, kojic acid, and licorice root extract, work in the same way as hydroquinone (tyrosinase inhibitors that inhibit the activity of tyrosinase enzyme to modulate melanin production).

Flavonoid arbutin and fungi-produced kojic acid are both natural, gentle, and safe alternatives to hydroquinone- without the notorious side effects and safety concerns. Licorice root extract has long been used in East Asian countries and contains several flavonoids (glabridine, glabrene, liquiritin and isoliquirtin) that fight hyperpigmentation. View Appendix A to have a look at these 3 depigmenting agents in detail.

While each of these ingredients alone may be weaker tyrosinase inhibitors than hydroquinone, research studies have shown that combining multiple weaker tyrosinase inhibitors together can have synergistic effects wherein the combination is significantly stronger than each alone. In short, through synergy, we can make 1+1+1 = 5. Such combinations have been shown in clinical trials to match or beat hydroquinone in effectiveness without the irritation (Boo 2021, Chandorkar et al. 2021, Choi et al. 2002, Hollinger et al. 2018, Woolery-Lloyd and Kammer. 2011).


Step 2: reinforce short-term treatment with long-term prevention

Having a treatment option is great, but preventing the problem from coming back would be even better!

Using depigmenting agents alone would be like scooping water out of a pail, while inflammation and UV damage continuously add water to the pail. Could we also stop additional water from flowing into the pail? In other words, what can we do to reduce the chance of hyperpigmentation from happening in the first place?

We again decided the answer was yes, and to do so, we again relied on a hyper-combination approach. Fade Away serum includes 14 botanical extracts with over 40 known phyto compounds that fight inflammation and UV damage as well as anti-inflammatory red algae extract and the antioxidant glutathione.

These anti-inflammatory and antioxidant ingredients can benefit the skin long-term, and ward off the inflammation and UV damage that are the two main contributing factors to hyperpigmentation.

Past studies show that non-toxic agents (that can include plant-based, marine-based, and non-toxic antioxidants, anti-inflammatories, and lightening agents) can actually synergize with one another to be more effective than hydroquinone based therapies, but without the harmful side effects (Boo 2021, Chandorkar et al. 2021, Choi et al. 2002, Hollinger et al. 2018, Woolery-Lloyd and Kammer. 2011).

Technically speaking: Fade-Away serum has 14 botanical extracts with over 40 known phyto compounds, marine red algae extract, and glutathione to prevent inflammation and UV damage- the main causes of future epidermal and dermal hyperpigmentation. These botanicals include plant oils such as moringa oleifera seed oil, sunflower seed oil, and thyme oil, and plant extracts such as turmeric leaf extract, neem flower and leaf extract, ocimum sanctum leaf (holy basil) leaf extract, cucumber fruit extract, rosemary leaf extract, coccinia indica fruit (ivy gourd) extract, and solanum melongena (eggplant) fruit extract. Aloe and witch hazel round out the botanical blend along with corallina officinalis (red algae) extract and powerful antioxidant glutathione.

These botanicals, long used throughout cultures for skincare, are known to contain powerful phyto compounds that have anti-inflammatory and antioxidant properties and include ferulic acid, quercetin, zeatin, curcumin, carnosic acid, carnosol, eucalyptol, eugenol, luteolin, gallic acid, aloe-emodin, aloin, acemannan, sesamol, carvacrol, thymol, linalool, camphor, borneol, oleonolic acid, ursolic acid, rosmaric acid, azadirachtin, nimbidol, nimbolinin, nimbin, nimbidin, gedunin, salannin, beta-sitosterol, glycyrrhixin, licochalcone A, caffeic acid, chlorogenic acid, oleanolic acid, and a host of other polyphenols and flavonoids that have been scientifically shown to prevent inflammation and neutralize free radical activity.

Red algae extract also contains marine compounds that have not yet been fully identified, but have been tested for their anti-inflammatory and antioxidant properties. Glutathione is a powerful antioxidant, typically produced in cells that has been shown to brighten skin. As FadeAway serum can be used as a standalone product, general humectant and moisturizing ingredients such as sodium hyaluronate and glycerin are added to ensure the serum is hydrating.


Having your cake and eating it too: our pursuit of maximum effectiveness with minimal irritation

The Maelove approach is to maximize effectiveness while keeping the overall treatment gentle enough for 99% of the population.

In making Fade Away, the formulation process behind making this unique and complex serum was a difficult undertaking. It took years to find the right combination of effective botanicals and other ingredients that worked well with the depigmentation trio (arbutin, kojic acid and licorice extracts), while also keeping the formula shelf stable.

This is where our experience in making our Love 31 face oil and Moonlight retinaldehyde serum came in handy! And we’re continuing to build on our knowhow of engineering exceedingly intricate formulas.

To summarize: Maelove Fade Away Serum has a unique combination of anti-hyperpigmentation, anti-inflammatory, and antioxidant ingredients, to create a synergistic and non-toxic blend that can both treat existing hyperpigmentation and prevent future hyperpigmentation. Additionally, this innovative formula can be used long-term while simultaneously being beneficial for general long-term skin health.


Combining Fade Away serum with other Maelove serums

While Fade Away is formulated to be highly effective as a standalone treatment that is safe to use long-term, the hyperpigmentation fighting abilities of Fade Away serum can be enhanced by combining it with other serums in the Maelove range of products.

In the same way that hydroquinone is combined with a tretinoin (a retinoid) to be more effective in the Kligman Formula, incorporating our Moonlight Retinal (retinaldehyde) serum in your routine can potentiate Fade Away serum to be more effective.

Retinal is known to be as effective as tretinoin while being less irritating. In addition to having lightening properties, retinoids can increase epidermal turnover to clear existing epidermal hyperpigmentation (see Newsletter 3). Particularly for those who have acne which can lead to PIH, it is necessary to first treat the acne- and retinoids can be highly effective against acne. Nonetheless, as retinoids are not generally recommended for use in pregnant women nor tolerated by some with very sensitive skin, having the option to use Fade-Away alone or in combination with Moonlight Retinal offers versatility.

Similarly, Vitamin C as well as Niacinamide are known hyperpigmentation fighters, as well as having additional anti-aging, anti-inflammatory, and antioxidant properties (see Newsletter One and Four). Therefore, Glow Maker and Nia 10 Calming serums can also boost the overall effectiveness of your hyperpigmentation fighting routine led by Fade Away serum.

Finally, the exfoliative properties of hydroxy acids can increase epidermal turnover to clear existing epidermal hyperpigmentation (see Newsletter Two). Particularly for those with acne and ingrown hairs which can lead to PIH, hydroxy acids can help treat these conditions. Maelove offers several hydroxy acid products that can be combined with Fade-Away serum.


Recommended routine:

For those who want to see the clearest and quickest results, the following lineup is recommended in the following order:


  • Glow Maker serum - Vitamin C is not only a powerful antioxidant (along with Vitamin E and Ferulic acid) but also inhibits tyrosinase and so has lightening properties.
  • NIA 10 Calming serum - Niacinamide prevents transfer of melanin to keratinocytes and is also a powerful anti-inflammatory, which can help prevent hyperpigmentation from forming.
  • Fade Away Brightening serum - Formulated specifically to fight hyperpigmentation, includes a trio of the natural tyrosinase inhibitors (arbutin, kojic acid, licorice root extract) as well as a large host of natural antioxidants and anti-inflammatories.
  • A lightweight moisturizer like Plush Cream, followed by Sun Protector.


  • NIA 10 Niacinamide Calming serum.
  • Fade Away serum.
  • Moonlight Retinal Super Serum- Particularly for those with hyperpigmentation from acne, retinal (retinaldehyde) not only helps treat acne but also downregulates tyrosinase (tyrosinase synthesis inhibitor) and prevents transfer of melanin. It can also help increase epidermal turnover to clear existing epidermal hyperpigmentation faster.  If you're pregnant, replace Moonlight Retinal with Night Renewer Glycolic Acid night cream.
  • A cream to seal in the serums like Plush cream, One Cream or even Night Renewer (if your skin is already tolerant of retinoids and hydroxy acids).

The real secret ingredient for long-term success is consistency. So, pick well-made products that you enjoy and create a simple routine that you can stick to. You'll be able to see healthier and more evenly balanced skin within a month or two. You can click here to check out our Fade Away Brightening Serum.


Appendix A: Individual Ingredients

Kojic acid

Kojic acid is an antiobiotic produced by species of Penicillum and Asperigillus fungi (Briganti et al. 2003). It is the most intensively studied tyrosinase inhibitor and in addition to its use as a lightening agent, it has antioxidant activity and it is used as a food additive to prevent browning (Chang 2009). It was thought to work by chelating copper at the active site of the tyrosinase enzyme although a more recent study suggests it binds the active site of tyrosinase preventing substrates from binding, and acts like a mixed inhibitor of tyrosinase (Deri et al. 2016).

It works well when combined with other compounds. When combined with emblica extract and glycolic acid, the blend was found to be as effective as 4% hydroquinone in treating hyperpigmentation (Hollinger et al. 2018). Contact dermatitis is a common side effect however, as well as sensitization and erythema (Ebanks et al. 2009). The CIR ingredient panel deems kojic acid safe to use up to 1% concentration in OTC products with no problems for a developing fetus.


Flavonoids: Arbutin and derivatives

Arbutin is found in the leaves of the bearberry shrub or pear, cranberry, and blueberry plants, and it inhibits tyrosinase activity (Maeda and Fukuda 1996). It is a phenol like hydroquinone. Arbutin in nature predominantly exists in b-arbutin form. While arbutin demonstrates considerable antioxidant activity (Takebayashi et al. 2009), it is mostly used as a lightening agent. Derivatives a-arbutin and deoxyarbutin are synthesized and also inhibit tyrosinase. a-arbutin shows specificity for mammalian tyrosinase and its effect on human tyrosinase is the greatest in its class while displaying no cytotoxicity to cells even at high concentrations unlike hydroquinone (Sugimoto et al. 2004). a-arbutin compared to hydroquinone is also less irritating as shown in several clinical studies confirming its safety (Chandorkar et al. 2021). For this reason, alpha-arbutin is the ingredient of choice for lightening agents (Zhu and Gao 2008).

Deoxyarbutin in human clinical trials show efficacy that matches or even exceeds hydroquinone. However, it demonstrates cytotoxicity to cells and in fact, there is concern that deoxyarbutin can easily degrade to hydroquinone. Though there is an extent to which b-arbutin and a-arbutin can hydrolyze to hydroquinone, studies have shown this hydrolysis is not significant enough to be cytotoxic. For this reason, while b-arbutin and a-arbutin have been deemed safe to use by the scientific committee on consumer safety (SCCS) (Europe’s safety board) up to 2% for a-arbutin and up to 7% for b-arbutin, deoxyarbutin has been deemed unsafe (Boo 2021, Garcia-Jiminez et al. 2017).

Though perhaps not as effective as hydroquinone at matching concentrations, safer arbutin (b-arbutin and a-arbutin) formulations can synergize with other anti-tyrosinase compounds and in combination, even exceed the efficacy of hydroquinone while maintaining little to no side effects. Alone, arbutin has been shown to be effective in melasma and against solar lentigines. Synergies increase this effectiveness and have been described with aloesin from aloe vera (in the study, aloesin and arbutin each reduced UVR-hyperpigmentation by 34% and 43.5% respectively, but by 63.3% together) and with Vitamin C against human tyrosinase activity (Choi et al. 2002).

Combination creams have also been tested that have equaled or exceeded the anti-melanin effects of hydroquinone. These combinations include 4% a-arbutin with niacinamide and tranexamic acid that matched 4% hydroquinone efficacy, and one with arbutin, niacinamide, tranexamic acid, vitamin C, and epidermal growth factor that exceeded 4% hydroquinone efficacy (Boo 2021, Chandorkar et al. 2021).


Flavonoids: Licorice extract

The roots and seeds of the licorice plant contain several flavonoids that are lightening agents. These include Glabridine which has even greater tyrosinase inhibitory activity than kojic acid and higher depigmenting activity than arbutin (Chang 2009) and Isoliquirtin and Glabrene which also have anti-tyrosinase activity (Briganti et al. 2003, Zhu and Gao 2008). Glabridine can prevent UVB induced pigmentation and has additional anti-inflammatory effects (Sarker et al. 2013).

Finally, flavonoid Liquiritin in licorice extract improves hyperpigmentation in clinical trials though not through tyrosinase inhibition but rather through melanin dispersal and as an anti-inflammatory. Licorice extract has long been used for skin lightening in East Asian countries (David and Callender 2010). Licorice root extract has also been used in combination creams such as with retinol and antioxidants to yield a superior effect (see figure, reproduced from Woolery-Lloyd and Kammer. 2011).

hyperpigmented skin improves thanks to licorice extract



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