How to Lighten Pigmentation and Dark Spots with Skin Care

22 June 2022

How to Lighten Pigmentation and Dark Spots with Skin Care



I’ve been sharing a lot about sunscreens so now I’m going to focus on skincare basics for hyperpigmentation and dark spots. This review will take you through the basics of pigmentation formation, active ingredients that lighten dark spots pigmentation and an easy read two of the novel active ingredients that target pigmentation- Cyspera cream (Cysteamine) and Glutathione.


Although skincare may not give you results that are as obvious or quickly as with in-clinic treatments; knowing how to use your skincare wisely is a cost effective way to protect your skin.


Remember: Be patient! Your pigmentation took time to build up and so, it will also take time for the pigmentation to fade. Skin care is certainly helpful, but creams alone may not completely eradicate all your pigmentation woes. A faster and more effective treatment for pigmentation is a combination of Q-switch laser and chemical peels.


More about treating pigmentation with lasers and chemical peels in this post 10 Things to Know Before Having Lasers for Your Pigmentation and The Truth About Chemical Peels.


What is pigmentation?



Pigmentation refers to the colour of our skin and eyes; so strictly speaking pigmentation is not a disorder but an excessive amount of pigmentation (i.e. hyperpigmentation) or a lack of pigmentation (i.e. hypopigmentation) cause dermatological problems.


This review will focus on unwanted darks spots and blemishes i.e. hyperpigmentation.


How is pigmentation formed?


This is the technical and dry part but trust me, this is important for understanding how various types of pigmentation lightening treatments work.


(1) Melanin is first formed in cells called melanocytes and one of the crucial steps involves an enzyme called Tyrosinase. (2) After melanin is formed in the melanocytes, melanin is then transferred to the skin cells called keratinocytes.


Melanin in the skin is responsible for the pigmentation of our skin. Melanin is produced by cells called melanocytes located mainly in the epidermis of the skin. The key step in melanin formation is controlled by an enzyme called tyrosinase. Majority of pigment busters block tyrosinase and are known as tyrosinase inhibitors. Common examples of tyrosinase inhibitors are Kojic acid, azelaic acid, Cyspera and vitamin C (L-ascorbic acid).


In the last stage of pigmentation formation, the melanin synthesised by the melanocytes is transferred to the cells on the surface of the skin- i.e. melanin transfer.


What is the cause of pigmentation?


Causes of pigmentation


Sun exposure is a major trigger factor for almost all types of pigmentation. Hence, the importance of sun protection cannot be under emphasised. You can read about my sunscreen recommendations and reviews in Sunscreen Reviews: The Best, Worst and Unsafe Ones I’ve Tried; I hope that you will be able to find a sunscreen that you like to protect your skin against hyperpigmenation formation.


There are also other factors that affect melanin and hyperpigmentation formation. Genetic predisposition, hormones (including pregnancy and oral contraceptive pills) and medications, to name a few.


Skincare basics to bust pigmentation: Topical treatments and sunscreens


When it comes to using skincare to tackle unwanted pigmentation and blemishes; think of it as a three way strategy: (1) Protect from UV rays with sunscreen;  (2) Prevent new spots with antioxidants; and (3) lighten the dark marks and blemishes that have already formed.



Pigmentation lighteners lighten pigmentation that has formed but they do not prevent the recurrence or development of new blemishes and dark spots- that’s for your sunscreen and antioxidants.


So what types of skincare ingredients should you look for to lighten your dark spots? This is where we dive into the gist of this blogpost. Read on!


Topical treatments: Tyrosinase inhibitors


Some of the pigmentation lighteners that I’m currently rotating through- I use a mixture of Tyrosinase inhibitors and Niacinamide.


The most common active ingredients that get rid of unwanted pigmentation are the tyrosinase inhibitors. You might be familiar with some of these commonly used tyrosinase inhibitors such as L-ascorbic acid (vitamin C), kojic acid, arbutin, azelaic acid and perennial favourite ingredient of Korean skincare, ginseng.  Tyrosinase inhibitors work by exactly how their names suggest- by blocking the activity of the key enzyme (tyrosinase) in the production of melanin.


One of the most common ways to lighten pigmentation is with Tyrosinase inhibitors.


One tyrosinase inhibitors that is considered to be the gold standard for pigmentation lightening is hydroquinone. In Singapore, hydroquinone can only be obtained with a doctor’s prescription. Hyroquinone is commonly available in combination with a steroid and tretinoin as a medication called Tri-luma. Despite its efficacy, hydroquinone is not without its problems. This is why doctors tend not to prescribe hydroquinone for more than 4 months.


Related blogpost:

5 Affordable & Popular Retinoid Serums Reviewed

The Beginner’s Guide to Starting Retinoids


All active ingredients and medications come with their own side effects and my preference for a topical lightening ingredients are L-ascorbic acid (vitamin C) and azelaic acid. I personally use them because both are relatively safe (even for pregnant and nursing mothers) with very little side effects.


More about how vitamin C and Azelaic acid work and how you can incorporate it in your skincare routine in All About Vitamin C: One of the Best Ways to Protect Your Skin  and Azelaic Acid: A Multitasking Skincare Active to Know.


Topical treatments: Inhibition of melanin transfer


Stopping the transfer of melanin is another way to lighten pigmentation.


Besides stopping the formation of melanin, another method to treat pigmentation would be to stop the transfer of the pigments (i.e. melanin) to the surface of the skin. Unfortunately, the mechanisms of melanin transfer are not as well understood as that of tyrosinase inhibition1.


There is one well known melanin transfer inhibitor that you can get over the counter (OTC) in skincare- Niacinamide or vitamin B3. I’ve written a blog post on Niacinamide before. Niacinamide is a versatile skincare ingredient that is suitable for sensitive and acne- prone skin. For the low down on Niacinamide and my reviews on some OTC Niacinamide skincare, please read this post Niacinamide: A Versatile Skincare Ingredient.


What’s New: The Latest Trends in Home Remedies for Lightening Pigmentation and Blemishes


There are a few novel skincare ingredients that look set to be potential powerful pigmentation busters that have been launched in Singapore very recently.  Let’s move on to a review of two of the more exciting pigmentation correctors- Cyspera (Cysteamine) and Glutathione.


Cyspera cream (Cysteamine) Review:

Cyspera cream (Cysteamine), an intensive pigment corrector, just hit the sunny shores of Singapore a few months ago this year after receiving Singapore’s HSA approval for commercial use.


Cyspera cream (Cysteamine)/ Cyspera Intensive Pigment Corrector- the latest lightening medication in Singapore. I’ve been asked to review Cyspera; but I can only try this after I am done with breastfeeding my newborn.


What is Cyspera cream (Cysteamine)/ Cyspera Intensive Pigment Corrector?


Cyspera is the product name of a new skin pigmentation lightening cream from Scientis Pharma for hyperpigmentation conditions like melasma and lentigenes.’The active ingredient of Cyspera is an antioxidant called Cysteamine.


Cysteamine is naturally present in the cells of our bodies and functions as an antioxidant to protect our cells from free radical damage to cell DNA, proteins and other cell structures which can potentially lead to cancer.


In the last 50 years, cysteamine has been shown to lighten pigmentation in the skin through several mechanisms 2-4. However, because of its offensive sulfur odor, cysteamine was never manufactured commercially for use in topical skincare.


What makes Cyspera (Cysteamine) worthy of note is that it is the first topical form of Cysteamine hydrochloride that has the odor removed.


How does Cyspera (Cysteamine) work?


Cysteamine has a long history of being used to treat various diseases including cystinosis (a rare genetic condition) and neurodegenerative disorders5. Cysteamine is also currently being studied to treat other conditions such as cancer, malaria and non-alcoholic fatty liver disease5.


In its current form as Cyspera cream to treat hyperpigmentation disorders, Cysteamine can be thought of as an old drug with new potential!


The mechanisms through which Cyspera cream (cysteamine) lighten pigmentation,melasma, have not been fully elucidated. However, the postulated mechanisms are:

1. Inhibition of tyrosinase and peroxidase enzymes6

2. Increasing glutathione (another antioxidant and lightening agent that will be covered in this post) levels in the cell7

3. Scavenging and removing dopaquinone8 (another substance involved in the synthesis of melanin/ pigmentation)

4. Chelate iron and copper ions which regulate the pigmentation synthesis pathway9


cyspera results


What are the benefits of using Cyspera (Cysteamine)?


Namely pigmentation lightening. Cyspera cream has been marketed heavily as ‘novel pigmentation corrector’ for pigmentation problems, especially melasma. Like most of the skin lightening ingredients that are commercially available; it is mostly a tyrosinase inhibitor.


Cyspera cream is the first and only topical formulation of cysteamine and it seems like a promising addition to the arsenal of depigmentation creams that are already available.


Is it safe to use Cyspera cream (Cysteamine)? What are the side effects of using Cyspera cream (Cysteamine)?


So far, Cyspera cream (cysteamine hydrochloride) has been shown to be very safe; with no risk of causing cancer, skin thinning, skin peeling or worsening of pigmentation- that may be encountered with other pigmentation lightening ingredients like hydroquinone and corticosteroids.


The common side effects that occur with applying Cyspera cream (cysteamine hydrochloride) are related to skin irritation (redness, itching and dryness)10. These side effects of Cyspera  creamwere also shown to be temporary10.


How soon can i see results of Cyspera/ cysteamine pigmentation cream?


Initial results can be seen 6 weeks of daily use of Cyspera/ cysteamine pigmentation cream for 15 minutes to the areas of hyperpigmentation. At 12 weeks, there is significant correction of pigmentation with 77% reduction in pigmentation10. 90% of users reported moderate to significant improvement in their pigmentation10.



Instructions for using Cyspera.


How do I use Cyspera/ Cysteamine cream?

Intensive phase: Once per day for 16 weeks

Maintenance phase: Twice-weekly, once per day


Apply Cyspera/ cysteamine cream on a rested skin i.e. Do not wash the skin before application. If necessary to wash, wait for one hour before application. This may sound counter intuitive to conventional use of skincare where skincare products are applied to clean and washed skin. Cyspera is applied on rested skin to minimise skin irritation.


Apply a thin layer on the skin (a warming sensation or mild tingling may occur and last up to 30 minutes). Leave on for 15 minutes and then wash off with a gentle face cleanser. Moisturise skin thereafter.


Can I use Cyspera cream (Cysteamine) if I am pregnant or breastfeeding?


Safety studies for pregnant and breastfeeding mothers have not been conducted for Cyspera/ cysteamine- so the data on this is still lacking. Based on the results from animal studies, oral cysteamine is classified as pregnancy category C; because cysteamine has been shown to cause fetal malformations and growth retardation in rats11.


As the topical form of cysteamine, Cyspera cream, may or may not share the same risks during pregnancy in humans; but my advice is NOT to use Cyspera cream when you are wanting to conceive or are currently pregnant or breastfeeding. Better to be safe than sorry; especially when there are other safer options for pigmentation lightening ingredients during pregnancy and breastfeeding like vitamin C (L-ascorbic acid) and Niacinamide.


Update: Where can I get Can I use Cyspera cream/ (Cysteamine)/ Cyspera Intensive Pigment Corrector?


In Singapore, Cyspera cream/ Cysteamine can only be purchased at clinics. Scientis Pharma, the manufacturer or Csypera cream/ Csyteamine has announced that it will be launched in the US this year.


My thoughts on Cyspera cream (Cysteamine)


It is certainly exciting to have a new player on the block for pigmentation treatment; as to whether it is truly the best treatment for melasma (as it is currently been marketed as)- we will have to await more studies. For now, it seems to be a promising and safe cream for treating pigmentation and may be a good alternative for patients with melasma other types of pigmentation that are hesitant to use hydroquinone.





What is glutathione?


Another power antioxidant in our bodies frequently mentioned in news reports and the media (but not necessary for the right reasons) is glutathione. Even celebrity doctor, Dr Oz, calls glutathione the “master antioxidant”.


Just like its antioxidant counterparts like cysteamine and vitamin C, glutathione help to counteract free radical damage to the cells; which is essential to preventing cancers from forming.


You might recall that I have briefly mentioned the use of Glutathione in the Skinbooster cocktails in this post Skinboosters: All You Need to Know About It– . However, did you know that glutathione can be given through an intravenous (IV) drip (i.e. whitening drip)? Whitening IV drips are banned in Singapore; however they are allowed and are very popular in countries like Korea, Taiwan, Thailand, Malaysia and the Philippines.


IV whitening drips and IV glutathione are beyond the scope of this blog post which aims to focus on topical skincare ingredients for lightening of pigmentation. So let’s focus on glutathione as a skincare ingredient.


How does glutathione lighten the skin or pigmentation?


Glutathione lightens the pigmentation via several mechanisms and one of them is by inhibiting the enzyme tyrosinase12-14, just like cysteamine and kojic acid.


The efficacy for topical glutathione is so far limited; with only one study to date- it shows that topical glutathione is generally safe with subjects reporting whiter skin after 10 weeks of use of glutathione skincare15. In Singapore, glutathione in skincare, oral supplements and intradermal injections (as part of Skinboosters) are allowed. IV glutathione or whitening drips  for skin lightening/bleaching are not permitted in Singapore. Glutathione in skincare care products can be bought over the counter in Singapore.


dr jart brightening mask


I found a brightening mask from Korean brand, Dr Jart, that contains glutathione as the star ingredient. I’ll be sharing my review of this glutathione mask soon!


Where can I find skincare products that contain glutathione?


Cult skincare brands like Dr. Barbara Sturm and Huxley carry products in their ranges that contain glutathione. Compared to oral glutathione supplements, skincare products that contain glutathione is much harder to come by.


My take on skincare containing glutathione


Although the data for topical glutathione is lacking; topical glutathione seems like a safe antioxidant to try as we wait for more studies on glutathione to be published. There is no harm trying glutathione containing skincare, although I would prefer sticking to other more well established lighteners like vitamin C, Niacinamide, azelaic acid and Cyspera.


Bottom Line on Treating Pigmentation With Skincare


So there you have it! I hope that you found this guide helpful to decoding your pigmentation busting skincare ingredients the next time you shop for them!


I’ll leave you with a few tips for pigmentation lightening in your daily skincare regimen:


1. Be patient- pigmentation builds up gradually. Likewise, fading unwanted pigmentation does not happen overnight- if you are looking for faster and better results; consider in-clinic treatments like chemical peels and lasers.

2. Combine your pigmentation busters. Pair an ingredient that is a tyrosinase inhibitor with a melanin transfer inhibitor (i.e. niacinamide).

3. Sunscreen always; you don’t want your pigmentation lightening efforts to be wasted. Pigmentation almost always recurs if there is inadequate sun protection.

4. Don’t forget your daily dose of antioxidants! Some antioxidants also double up as pigmentation busters; so consider using these multitasking ingredients.


If you enjoyed this post; you might also enjoying reading these skincare related blogposts:

Everything You Need to Know About Hyaluronic Acid

All About Topical Vitamin C

Niacinamide: A Versatile Skincare Ingredient Your Skin Will Thank You For

Is Profhilo the future of Injectable Skincare? 

Probiotics in Skincare and Supplements: Do They Work?

Ceramides: A Relief for Sensitive & Dry Skin, Eczema and Premature Aging

Is Bakuchiol An Effective Retinol Alternative?

  REFERENCES   1. Cellular mechanisms regulating human melanogenesis. Park et al. Cell Mol Life Sci. 2009;66:1493–506. 2. A new series of depigmentational agents in the black goldfish. Chavin. Naturwissenschaften. 1966;53:163. 3. Some potent melanin depigmentary agents in the black goldfish. Chavin and Schlesinger. Naturwissenschaften. 1966;53:413-414. 4. Selective action of mercaptoethylamines on melanocytes in mammalian skin: experimental depigmentation. Frenk et al. Arch Dermatol. 1968;97:465-477. 5. Cysteamine: an old drug with new potential. Besouw et al. Drug Discov Today. 2013 Aug;18(15-16):785-92. 6. Peroxidase-mediated mechanisms are involved in the melanocytotoxic and melanogenesis-inhibiting effects of chemical agents. Kasraee B. Dermatology 2002; 205:329–39. 7. The importance of having high glutathione (GSH) level after bovine in vitro maturation on embryo development: effect of beta-mercaptoethanol, cysteine and cystine. de Matos and Furnus.Theriogenology 2000; 53:761–71. 8. Cysteine-dependent 5-S-cysteinyldopa formation and its regulation by glutathione in normal epidermal melanocytes.Benathan and Labidi. Arch Dermatol Res 1996; 288:697–702. 9. Non-melanosomal regulatory factors in melanogenesis. Shibata et al. J Invest Dermatol 1993; 100:274S–80S. 10. Evaluation of the efficacy of cysteamine 5% cream in the treatment of epidermal melasma: a randomized double-blind placebo-controlled trial. Mansouri et al. Br J Dermatol. 2015 Jul;173(1):209-17 11. Developmental toxicity of cysteamine in the rat: effects on embryo-fetal development. Beckman et al. Teratology 1998; 58, 96–102. 12. Glutathione as a depigmenting agent: an overview. Villarama and Maibach. Int J Cosmet Sci 2005; 27: 147–153. 13. Glutathione as an oral whitening agent: a randomized, double-blind, placebo controlled study. Arjinpathana and Asawanonda. J Dermatolog Treat 2012; 23: 97–102. 14. Mechanisms regulating skin pigmentation: the rise and fall of complexion. Ebanks et al. Int J Mol Sci. 2009 Sep 15;10(9):4066-87. 15. Skin-whitening and skin-condition-improving effects of topical oxidized glutathione: a double-blind and placebo-controlled clinical trial in healthy women. Watanabe et al. Clin Cosmet Investig Dermatol. 2014 Oct 17;7:267-74.    



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