What are the skin lightening alternatives to hydroquinone?

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How to cite: Wong M. What are the skin lightening alternatives to hydroquinone?. Lab Muffin Beauty Science. April 20, 2014. Accessed April 22, 2024. https://labmuffin.com/what-are-the-skin-lightening-alternatives-to-hydroquinone/

Recently we looked closely at the most famous of the whitening agents, hydroquinone – it’s the most studied and very effective, but has some serious (though often overstated) side effects, is irritating to the skin, and has been heavily restricted in some countries as well. Today let’s have a look at some of the other whitening agents on the market – how do they work, and what are the side effects?

The most commonly used topical treatments for treating hyperpigmentation are usually hydroquinone or retinoids, which are quite irritating to the skin. Therefore a lot of people turn to alternative whitening agents. Although many of these haven’t been studied extensively, they appear in many products and appear to be quite safe.

Note that clinical studies are almost always done on patients who have quite severe hyperpigmentation, such as melasmas and dyschromias – not the target audience of this post (if your hyperpigmentation is severe, you should discuss your specific situation and treatment options with a dermatologist). This means that the results mightn’t entirely translate to the mild freckling, acne scarring and sun damage that the average beauty junkie is looking to reduce.

How do lightening products work?

Whitening agents work in a number of different ways, and some work in more than one way. Lightening products generally slow down melanin production.

Most treatments for hyperpigmentation act on the first step of melanin synthesis – the conversion of tyrosine into DOPA and dopaquinone by an enzyme called tyrosinase. They can either:

  1. act as a mimic of tyrosine, essentially keeping tyrosinase too busy to produce as much melanin as before (hydroquinone, mequinol, azelaic acid, arbutin, licorice extract)
  2. block off the important copper ions in tyrosinase, preventing the enzyme from working (kojic acid)

Some other ways ingredients reverse or slow down hyperpigmentation are:

  • slowing down the production of tyrosinase enzyme (N-acetylglucosamine)
  • undoing the reaction that tyrosinase does (ascorbic acid)
  • slowing down maturation of melanosomes (pigment producing organelles) (arbutin and derivatives)
  • preventing melanin pigment from travelling from the melanocytes where it’s made, to the keratinocyte skin cells (soy, niacinamide, retinoids)
  • dispersing pigment (licorice extract)
  • increasing skin turnover, meaning there are more skin cells being produced, and less pigment to go around (alpha and beta hydroxy acids, retinoids)

In general, side effects are less of a concern for the less effective ingredients; however, combining different whitening agents results in a more potent product without too much irritation.

Mequinol (4-Hydroxyanisole)

Mequinol is the main alternative prescription alternative to hydroquinone. It’s also known as methoxyphenol, hydroquinone monomethyl ether, and p-hydroxyanisole.

How it works: It’s not entirely clear how mequinol works, but it seems that it’s similar to hydroquinone in that it mimics tyrosine and decreases tyrosinase’s ability to make melanin pigment.

Strength: Mequinol usually comes at a concentration of 2%, sometimes in combination with 0.01% tretinoin and ascorbic acid to enhance penetration. It’s been found to be as effective as hydroquinone.

Irritation potential and side effects: It’s supposed to be less irritating than hydroquinone, but can sometimes cause temporary postinflammatory hyperpigmentation. There has also been some instances of reversible depigmentation.


Retinoids are analogues of vitamin A, used for treating many conditions such as acne and sun damage, as well as acting as a penetration enhancer for other treatments. Examples include tretinoin, adapalene, tazarotene and isotretinoin, as well as retinol, which is available over the counter.

How it works: Retinoids are thought to work in multiple ways to reduce pigmentation, including increasing skin turnover, interfering with transfer of melanin to the skin, reducing the amount of tyrosinase produced in the skin and dispersing melanin. Retinoids are usually used in combination with other treatments for hyperpigmentation – by themselves, they take several months to achieve results.

Strength: Commonly used strengths of retinoids vary according to the retinoid in question: tretinoin (0.05—0.1%), adapalene (0.1—0.3%), tazarotene (0.01—0.1%), retinol (up to 4%). They’re also commonly combined with corticosteroids to reduce irritation and the chances of postinflammatory hyperpigmentation.

Irritation potential and side effects: Different retinoids have different irritation potential – in general, the more effective the retinoid, the more irritating and more side effects it will have. Retinoid irritation is common and leads to redness, dryness and peeling (which is also why it works well as a penetration enhancer). Postinflammatory hyperpigmentation is also a risk, especially in darker skin. Adapalene is one of the less irritating retinoids.

Azelaic acid

Azelaic acid is another common alternative to hydroquinone and is a prescription-only acne treatment in many countries. It’s produced by a fungus, Pityrosporum ovale, which sometimes infects humans and causes light patches on the skin. It is slightly milder than hydroquinone, but in combination with retinoids has been as effective as 4% hydroquinone, with less side effects.

How it works: Azelaic acid interferes with tyrosinase activity as a tyrosine mimic, and suppresses and kills abnormal melanocytes.

Strength: 15-20%, sometimes combined with glycolic acid.

Side effects: Azelaic acid is known for the lack of side effects with its use – the main side effects are mild stinging and redness.


Arbutin is sometimes known as “natural hydroquinone” since its structure is very similar to that of hydroquinone. It’s found in extracts of bearberry leaves, and to a lesser extent in cranberry and blueberry leaves as well. Two synthetic forms of arbutin, alpha-arbutin and deoxyarbutin, are more potent than arbutin itself.

How it works: Arbutin slowly turns into hydroquinone, acting as a tyrosine mimic to slow down the production of melanin. It also interferes with the maturation of melanosomes, organelles responsible for melanin production.

Strength: There are few clinical studies on arbutin’s efficacy as a lightener, and some of those that have been published have reported mixed results. One trial found that deoxyarbutin-induced lightening was maintained when hydroquinone-induced lightening was not. 5% is commonly used, though higher concentration formulations exist.

Side effects: Higher concentrations run the risk of postinflammatory hyperpigmentation.

Kojic acid

Kojic acid is produced by bacteria in the fermentation of rice in the manufacture of sake (Japanese wine). A derivative of kojic acid, kojyl-APPA, has also been investigated for its whitening effect and improved skin penetration.

How it works: Kojic acid binds to copper in tyrosinase, preventing it from performing its role in the production of melanin.

Strength: Kojic acid is usually found at 1-4% concentrations, often in combination with hydroquinone, retinoids, glycolic acid, emblica extract or corticosteroids.

Side effects: Kojic acid is very irritating, and can be combined with a corticosteroid to reduce the chances of a reaction. It is also a potential allergen.

Licorice extract

An extract from the root of the licorice plant (Glycyrrhiza glabra) is popularly used as a whitening ingredient in cosmetics. It contains a number of antioxidant and anti-inflammatory chemicals, as well as the major whitening components, glabridin and liquirtin (and a range of other related flavonoids). However, not many clinical studies on these extracts exist, although the one trial with liquirtin showed good results.

How it works: Glabridin protects skin from UVB-induced pigmentation, as well as acting on tyrosinase to slow down melanin production. Liquirtin disperses melanin.

Strength: Glabridin creams contain 10-40%, while liquirtin has been tested as a 20% cream.

Side effects: Licorice extracts are mild and have few side effects, thought to be due to its anti-inflammatory and anti-irritant ingredients.

Ascorbic acid (Vitamin C)

Vitamin C is an ingredient in many skincare products, due to its potent antioxidant activity. However, it is very unstable and is usually combined with other ingredients.

How it works: Ascorbic acid turns dopaquinone back into L-DOPA, undoing the reaction that tyrosinase does.

Strength: Ascorbic acid is typically found in 5-10% concentrations. A trial of 5% ascorbic acid was found to be less effective than 4% hydroquinone, but was significantly less irritating.

Side effects: Ascorbic acid has an excellent safety profile, with much less irritating potential than many other lightening agents.

Soy proteins

Soy proteins are extracted from soybeans. The most studied lightening agent in soy is soybean trypsin inhibitor.

How it works: Soybean trypsin inhibitor interferes with the transfer of pigment from the melanin-producing cells to the skin. It is not as effective as hydroquinone.

Side effects: The lightening action of soy is reversible and the side effects are minimal.


N-Acetylglucosamine is a sugar found throughout nature and in the body, and is a precursor of hyaluronic acid.

How it works: Slows down the production of tyrosinase enzymes, essential in the synthesis of melanin.

Strength: 2% N-acetylglucosamine has been found to improve pigmentation in clinical studies, and is frequently used in conjunction with niacinamide.

Side effects: Mild to moderate skin irritation sometimes occurs.


Niacinamide, also known as nicotinamide and vitamin B3, is found in many plants. It is an antioxidant, and is very stable.

How it works: Niacinamide inhibits transfer of pigment to the skin.

Strength: 2-5% is the typical concentration, and has been found to be effective in reducing hyperpigmentation in several studies, although it is usually combined with other agents.

Side effects: Some skin irritation can occur.


If you’re wary of hydroquinone, or your skin can’t handle it, there are still plenty of options for treatment of hyperpigmentation.



JJ Leyden, B Shergill, G Micali, J Downie and W Wallo, Natural options for the management of hyperpigmentation, J Eur Acad Dermatol Venereol 2011, 25, 1140.

VM Sheth and AG Pandya, Melasma: A comprehensive update: Part II, J Amer Acad Dermatol 2011, 65, 715.

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13 thoughts on “What are the skin lightening alternatives to hydroquinone?”

  1. Latecomer to this one (oops!). Do you know if there are any lighteners/treatments for post-inflammatory hyperpigmentation (redness, mostly) that will leave freckles alone? I’ve got some acne marks I’d like to fade, but I’m rather fond of my freckles right now!

    • Unfortunately I don’t think there’s anything that will leave them completely alone, but you might have some luck with things like AHAs and retinol, which don’t specifically target the pigment but mainly increase skin turnover.

    • Cheers 🙂 I suspected that might be the case. My skin is pretty sensitive to strong active ingredients and has flipped out over glycolic acid in the past so I’m hesitant to try anything with irritation potential.

  2. You mentioned in another post that you add a few drops of Rosehip oil to your moisturizer. I’ve seen a bottle of Licorice extract floating around at my local health store, so I was wondering would it be ok to treat Licorice extract in the same way (and put a few drops of that in my moisturizer)? Thanks!

  3. Good job Michelle!! Very informative summary of a common skin subject, with good explanation of the science behind it.

  4. Michelle, I’ve spent hours swimming around your archives over the past few weeks and just love your writing. Can you do a post sometime about scar prevention? I don’t know if it’s due to being Asian or just getting older, but I now get hyperpigmentation just from papercuts. On the plus side, I’m thinking about giving myself a cool scarification tattoo, which will probably last 5 years based on what the scratch from a screen door did to my ankle. Your hydrocolloid bandage post was fascinating, and I’d love to learn more.


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