Skin Lightening Agent Combos That Pack a Serious Punch

I’ve already discussed the least favorable skin ingredient combinations in regard to skin lightening. In this post, I will shift the focus to the most favorable (or most efficacious, should I say) skin lightening ingredient combinations based on clinical research.

Sepiwhite (Undecylenoyl Phenylalanine) + Niacinamide

The combination of 5% niacinamide and 1% sepiwhite (N-undecylenoyl phenylalanine) has been shown to significantly reduce the appearance of hyperpigmentation in as little as 8 weeks.

This particular ingredient pairing creates a powerful synergistic skin lightening effect (greater than if these ingredients were used alone), since they target multiple points of melanin synthesis. Niacinamide inhibits melanosome transfer from melanocytes to keratinocytes and inhibits the pigment producing enzyme tyrosinase, while sepiwhite uniquely acts as an antagonist to the melanocyte stimulating hormone in addition to inhibiting tyrosinase. The result is more complete and efficacious melanin inhibition.

Arbutin + Aloesin

Arbutin and aloesin (a compound isolated from the aloe plant) produce a synergy in melanin suppression through their combined mechanisms of noncompetitive (aloesin) and competitive (arbutin) inhibition of tyrosinase activity.

Hydroquinone + Kojic Acid

Kojic acid, at concentrations of 2% to 4%, in combination with hydroquinone at concentrations of 2%, have demonstrated potent skin lightening effects, reaching maximum melanin inhibition status in vitro.

Vitamin C + Vitamin E

Skinceuticals C E Ferulic is a cult classic for good reason as it contains the powerfully effective combination of vitamin C, E, and ferulic acid.

Antioxidants vitamin C and vitamin E, when used together, have been shown to significantly improve melasma and pigmented contact dermatitis lesions. Additionally, this ingredient combination provides excellent UV photo protective benefits.

N-Acetyl Glucosamine + Niacinamide

2% N-Acetyl Glucosamine used in combination with 4% niacinamide produces significant skin lightening effects after 8 weeks of usage. Like many of the pairings mentioned in this post, this combination offers a greater skin lightening effect than if these ingredients were used alone or separately.

Azelaic Acid + Tretinoin

Combination therapy involving 20% azelaic acid and 0.05% or 0.1% tretinoin demonstrates superior skin lightening effects over the use of these ingredients by themselves. Tretinoin, which on its own, effectively disperses melanin deposition in the epidermis, enhances the efficacy of azelaic acid, which inhibits the energy production and/or DNA synthesis of hyperactive melanocytes, as well suppresses tyrosinase activity.

The use of both azelaic acid and tretinoin is effective and well-tolerated on darker skin types.

Hydroquinone + Kojic Acid + Glycolic Acid

The addition of 2% kojic acid to the well-established combination of 10% glycolic acid and 2% hydroquinone has been shown to substantially improve epidermal melasma. In general, using exfoliants like glycolic acid (which holds tyrosinase inhibiting benefits to a degree) with potent tyrosinase inhibitors such as hydroquinone and kojic acid effectively lighten skin, by breaking up existing and excess melanin while preventing the formation of new melanin.

Hydroquinone + Tretinoin

Tretinoin and hydroquinone lighten skin by removing existing epidermal pigmentation and preventing future melanin deposition. This combination is often supplemented with a third ingredient, typically a topical steroid (mometasone or dexamethasone) to mitigate potential irritation. This amalgamation is dubbed ‘Triple Topical Therapy‘ and has been shown to be effective and well-tolerated even in reactive and darker skinned individuals due to the anti-inflammatory benefits offered by the topical steroid.

Kojic Acid, Phytic Acid + Avobenzone (Butyl Methoxydibenzoylmethane)

In a double-blind, controlled comparative study, kojic acid, phytic acid and avobenzone (butyl methoxydibenzoylmethane were shown to effectively eliminate epidermal melasma.

Chemical Exfoliants + Plant Extracts

Plant extracts which inhibit melanogenesis such as licorice, bearberry, mulberry, rumex, soy, reservatol, flavanoids, polyphenols, and gigawhite are best used in conjunction with alpha hydroxy acids, beta hydroxy acids, and retinoids, since the latter enhances their penetration, which results in more effective skin lightening.

Best Products to Try

So, what are some skin lightening products that utilize one or more of these ingredient combinations for getting rid of dark spots, balancing out skin tone, and generally improving your overall complexion?

We personally recommend using the following skin whitening serums and creams for the best and quickest results possible:

Bottom Line

Combining a multitude of skin lightening ingredients to enhance penetration and interrupt the multiple key steps in melanogenesis can lead to powerful and novel treatment options which are far superior to monotherapy options.

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