10 Hydroquinone Alternatives

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Hydroquinone is one of the most famous whitening agents. It is most studied to date, and very effective. However, it does have some serious side effects, can be irritating to skin and has been heavily restricted in some countries. 

Today, we look at some of the other whitening agents on the market, how they work and what side effects they have. 


Whitening agents in the market work in a number of different ways, some in more than one way. But most will generally slow down the production of melanin, which is what gives our skin it’s colour and tone.

The agents available on the market generally work by acting on the first step of melanin synthesis – the conversion of tyrosine into DOPA and dopaquinone by an enzyme called tyrosinase. They work by either:

  • Acting as a mimic of tyrosine – essentially keeping tyrosinase too busy to produce as much melanin as before (hydroquinone, mequinol, azelaic acid, arbutin, licorice extract) 
  • Blocking off important copper ions in tyrosinase and thus preventing the enzyme from working (kojic acid) 

There are also other ingredients that can reverse or slow down hyperpigmentation using other pathways: 

  • Slowing down production of the tyrosinase enzyme (N-acetylglucosamine)
  • Reversing the reaction that tyrosinase does (ascorbic acid/Vitamin C)
  • Slowing down maturation of melanosomes (arbutin and derivatives)
  • Preventing melanin from travelling from melanocytes to skin cells (soy, niacinamide, retinoids)
  • Dispersing pigments (licorice extract)
  • Increasing skin turnover, meaning less pigments to go around (alpha and beta hydroxy acids, retinoids) 

There are also other ingredients that can reverse or slow down hyperpigmentation using other pathways:

In general, side effects are less of a concern for less effective ingredients, but combining different agents may result in a more potent product without too much irritation. 

Below, we investigate the agents individually: 

1. Mequinol

Mequinol is the main alternative prescription alternative to hydroquinone. It is not entirely clear how mequinol works, but it seems similar to hydroquinone in that it mimics tyrosine and decreases tyrosinase’s ability to produce melanin. It comes in concentrations of 2% and sometimes in combination with 0.01% tretinoin and ascorbic acid to enhance penetration.

It is supposed to be less irritating than hydroquinone but can sometimes cause temporary postinflammatory hyperpigmentation (PIH). Rarely, it can lead to reversible depigmentation. 

2. Retinoids

Retinoids are Vitamin A analogues used for treating many conditions such as acne, sun damage as well as acting as a penetration enhancer for other treatments. Examples are: tretinoin, adapalene, tazarotene, isotretinoin (prescription) and retinol (non-prescription).

Retinoids are thought to work in multiple pathways to reduce pigmentation, including increased skin turnover, interruption of melanin transfer to skin cells, reduced tyrosinase production in skin and dispersal of melanin. Retinoids are commonly used in combination with other treatments for hyperpigmentation as on their own, they can take several months to achieve results.

In general, the more effective a retinoid is, the more irritating its side effects. Common side effects include redness, dryness and peeling. PIH is also a risk, especially in darker skin. 

3. Azelaic Acid

Azelaic acid is another common alternative to hydroquinone. It is produced by a fungus which sometimes infects humans and causes light patches of skin. It is slightly milder than hydroquinone but in combination with retinoids, can come close to the effects of hydroquinone.

Azelaic acid works by interfering with tyrosinase activity as a tyrosine mimic, and suppresses and kills abnormal melanocytes. It is known for its lack of side effects, which are mild stinging and redness. 

4. Arbutin

Arbutin is sometimes also known as the “natural hydroquinone”. Its chemical structure is very similar to hydroquinone. It is found in extracts of bearberry leaves and to a lesser extent in cranberry and blueberry leaves.

It works in our bodies by slowly turning into hydroquinone and acting as a tyrosine mimic to slow down production of melanin. It also interferes with maturation of melanosomes. Results from studies on its efficacy are mixed.

The most common formulation is 5% although there are higher formulations. Higher concentrations of arbutin increase the risks of PIH. 

5. Kojic Acid

Kojic acid is produced by bacteria in the fermentation of rice in the manufacture of Sake.

A derivative of kojic acid, kojyl-APPA has also been investigated on its whitening effect and improved skin penetration. It works by binding to copper in tyrosinase, preventing the enzyme from performing its role in the production of melanin.

It is often combined with hydroquinone, retinoids, glycolic acid, emblica extract or corticosteroid. It is very irritating and is a potential allergen. Preparations typically include steroids to reduce the chances of a reaction. 

6. Licorice Extract

Licorice extract is extracted from the root of the licorice plant (Glycyrrhiza glabra) and is widely used as a whitening ingredient in cosmetics. It contains a number of antioxidants and anti-inflammatory chemicals. Its main effects are through two whitening components, glabridin and liquirtin.

Glabridin protects skin from UV-B induced pigmentation whilst also acting on tyrosinase to slow down melanin production. Liquirtin disperses melanin. Licorice extracts are mild and have few side effects, likely due to its anti-infammatory and anti-irritant ingredients. 

7. Ascorbic Acid (Vitamin C)

Vitamin C is an ingredient in many skincare products. It is a potent antioxidant, but is very unstable and is usually combined with other ingredients.

Vitamin C works by turning dopaquinone back into L-DOPA, undoing the reaction that tyrosinase does. It is less irritating than hydroquinone and has a good safety profile. 

8. N-Acetylglucosamine

N-acetylglucosamine is a sugar found abundantly in nature and is a precursor of hyaluronic acid. It works by slowing down the production of tyrosinase, which is a crucial enzyme in the synthesis of melanin.

It has been found to improve pigmentation at 2% in clinical studies and is often used in conjunction with niacinamide. It can cause mild to moderate skin irritation occasionally. 

9. Niacinamide

Niacinamide is also known as nicotinamide and Vitamin B3. It is an antioxidant but unlike vitamin C, it is very stable. It works by inhibiting the transfer of pigments to skin cells. 2-5% is the typical concentration and has been found to be effective in reducing hyperpigmentation in several studies. Some skin irritation can occur. 

10. Cysteamine

Cysteamine is a new kid on the block when it comes to pigments. It is a chemical compound that can be biosynthesized in mammals (this includes humans) by degradation of co-enzyme A. It was conventionally used as a treatment for cystinosis.

Recently, ScientisPharma had compounded it into a 5% cream for treatment of hyperpigmentation and to lighten skin overall. Cysteamine is a metabolite of L-cysteine which inhibits melanin synthesis. The ways it is thought to work through includes inhibition of tyrosinase and peroxidase, scavenging of dopaquinone, chelation of iron and copper ions and increasing intracellular glutathione.

Randomized controlled trials have confirmed the efficacy of cysteamine cream in treatment of epidermal melasma, a hyperpigmentation disorder. Side effects are generally mild, with temporary heating up or burning sensation and redness that is typically short-lived. 

In Conclusion

That is 10 alternatives to hydroquinone for hyperpigmentary disorders, all with different modes of action. If you are wary of hydroquinone, or your skin cannot handle it, there are still plenty of options for treatment of hyperpigmentation. Feel free to speak to your doctor if you have concerns with hydroquinone or if there is pigmentation on your face that you are concerned about. 

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