Which active ingredients should glycolic acid be combined with?

The combination of glycolic acid with retinoids is based on the complementarity of their mechanisms of action. Retinoids, whether in the form of retinol, retinal, or retinoic acid, are vitamin A derivatives known for their ability to normalize cell turnover, reduce inflammation, and stimulate collagen synthesis, making them particularly effective for reducing blemishes and fading acne scars. By combining the keratolytic effects of glycolic acid with those of retinoids, one achieves a notable synergy for acne-prone skin or skin with pigmentary irregularities.

A twelve-week study evaluated the efficacy of a combination of glycolic acid (12%) and retinoic acid (0.025%) in 35 patients aged 17 to 34 with acne scarring. The results showed a significant improvement in scarring in 91.4% of the patients, demonstrating that this combination can effectively reduce the appearance of acne scars and may limit the need for more invasive treatments.

Although combining glycolic acid with retinoids is effective, we do not recommend this combination for sensitive skin.

The bakuchiol is a plant-derived active ingredient often described as a gentle alternative to retinol. It promotes cell turnover, stimulates collagen synthesis, and has antioxidant and anti-inflammatory properties, which helps improve the appearance of fine lines, uneven skin texture, and pigmentation spots. When combined with glycolic acid, the bakuchiol may potentiate the effects of exfoliation and cell renewal without increasing the irritation risks commonly associated with this AHA. This combination therefore appears promising for smoothing the skin and evening out the complexion.

Although combining glycolic acid and bakuchiol may be theoretically appealing, no clinical trial to date has evaluated the efficacy or tolerability of this combination.

The benzoyl peroxide is an essential active ingredient in acne management due to its antibacterial properties, which are particularly effective against Cutibacterium acnes, the bacteria involved in acne exacerbation. It also has an exfoliating effect and helps reduce skin inflammation. Combining benzoyl peroxide and glycolic acid could theoretically be relevant for reducing blemishes, whether open or closed comedones or inflammatory lesions (papules and pustules). However, no study has investigated the combination of glycolic acid and benzoyl peroxide, and the potential irritancy of these two actives remains a significant limitation.

We advise against the simultaneous use of glycolic acid and benzoyl peroxide products, as this may irritate your skin.

Azelaicacid is a dicarboxylic acid widely used in dermatology for its anti-inflammatory, antibacterial, and depigmenting effects. It is particularly useful for managing mild acne or rosacea, where it works by reducing the proliferation of Cutibacterium acnes and by soothing the skin. Azelaic acid is also known for its effect on post-inflammatory hyperpigmentation and melasma, thanks to its ability to inhibit tyrosinase, the enzyme responsible for converting tyrosine into melanin. When combined with glycolic acid, azelaic acid may help achieve a smoother, more even complexion.

Azelaic acid and glycolic acid can be beneficial for skin prone to blemishes and/or displaying pigmentary spots.

A study conducted on 70 patients with acne compared the efficacy and tolerability of a 20% azelaic acid cream combined with a 15% glycolic acid lotion to those of a 0.025% tretinoin solution. The 12-week protocol involved two daily applications, morning and evening, with dermatological follow-up. The results indicate that the azelaic acid/glycolic acid combination significantly reduced the number of acne lesions, showing efficacy comparable to tretinoin for non-inflammatory lesions and superior for inflammatory lesions. Moreover, the tolerability proved superior, with patients experiencing less dryness, redness, and flaking than with tretinoin.

The hyaluronic acid stands out for its exceptional moisturizing properties. Depending on its molecular weight, it can retain up to 1,000 times its weight in water within the extracellular matrix. As a flagship cosmetic active, the hyaluronic acid helps restore barrier function and minimize transepidermal water loss, delivering comfort and suppleness to the skin. Its combination with glycolic acid—known for its exfoliating action and potential irritancy—is therefore compelling: hyaluronic acid bolsters skin hydration, counteracting any sensations of tightness and reducing the risk of intolerance to glycolic acid without compromising its exfoliating benefits.

A clinical trial conducted on 100 patients with melasma evaluated several combinations of depigmenting treatments. Participants were divided into five groups: hydroquinone alone (group 1), hydroquinone plus glycolic acid (group 2), hydroquinone combined with hyaluronic acid (group 3), hydroquinone plus glycolic acid and hyaluronic acid (group 4), and a placebo group. After 12 weeks of daily application, the groups receiving hydroquinone alone, hydroquinone with hyaluronic acid, or the hydroquinone/glycolic acid/hyaluronic acid combination showed a notable improvement in the MASI score, reflecting a reduction in hyperpigmentation. At the same time, adding hyaluronic acid decreased the frequency and severity of adverse effects observed with glycolic acid alone, suggesting it enhances the tolerability of that agent.

Glycerin is one of the humectants most widely used in cosmetics, recognized for its ability to attract and retain water in the stratum corneum. It strengthens the skin’s barrier function, reduces dehydration and improves skin elasticity. Glycerin also has an occlusive effect. It forms a film on the epidermal surface that reduces water loss. In formulations, the glycerin often plays a protective role and is frequently used to counteract the irritating effects of certain active ingredients, such as glycolic acid, thereby ensuring better tolerance.

The combination of glycerin and glycolic acid is widely used in cosmetic formulations as it helps mitigate the side effects associated with glycolic acid while maintaining its exfoliating effectiveness.

The vitamin C, or ascorbic acid, is an active ingredient primarily known for its antioxidant and brightening properties. It neutralizes free radicals involved in oxidative stress while inhibiting tyrosinase activity, thereby reducing melanin production. This positions vitamin C as a key ingredient in addressing pigmentation spots and dull skin tone. In synergy with glycolic acid, which facilitates ingredient penetration by removing dead cells from the skin’s surface, vitamin C’s effects can be amplified, particularly in reducing hyperpigmentation.

A clinical study evaluated this combination for the management of melasma. The trial involved 178 patients with pronounced hyperpigmentation (MASI score > 10), divided into two groups. The first group received a 40% glycolic acid peel every two weeks, combined with the daily application of a vitamin C–based cream. The second group followed a standard protocol using a 4% hydroquinone cream combined with tretinoin and topical corticosteroids. After six weeks, the results showed a significantly greater improvement in the glycolic acid + vitamin C group, with a reduction in hyperpigmentation in 94.38% of participants, compared with 79.77% in the hydroquinone group. These data suggest that the combination of glycolic acid and vitamin C represents a promising option for attenuating pigmented spots.

The combination of glycolic acid and pure vitamin C can be too irritating for sensitive skin.

Niacinamide, also known as vitamin B3, is a versatile active ingredient widely used in cosmetics for its anti-inflammatory, hydrating, and brightening properties. It works notably by soothing redness and limiting the transfer of melanin to keratinocytes, which helps fade pigmentation spots. Moreover, it strengthens the skin barrier by stimulating ceramide synthesis, making it an excellent ally to offset the sensitivity sometimes associated with exfoliating acids. When combined with glycolic acid, niacinamide therefore improves both the efficacy and tolerability of this AHA.

A two-month prospective study involving 25 women with mild acne confirmed the benefit of this synergy. Participants applied a gel containing, among other ingredients, niacinamide and glycolic acid daily. After eight weeks, the results showed a nearly 80% reduction in the number of acne lesions and a significant improvement in the GAGS clinical score, used to evaluate acne severity. Analyses also revealed reduced inflammation and pigmentary disturbances. Finally, measurement of transepidermal water loss demonstrated that skin barrier function remained intact, underscoring the treatment's good tolerability despite the presence of an AHA.

Note : If some products are formulated to contain glycolic acid and niacinamide, layering two products with these actives can sometimes be counterproductive. For example, our glycolic acid exfoliating serum has a low pH of around 3 to 4, while our niacinamide unifying serum has a higher pH of approximately 5 to 7. If they are combined, the niacinamide will raise the pH of the glycolic acid serum, making it less effective.

The hydroquinone is considered a gold-standard depigmenting agent and is used in the treatment of hyperpigmentation and melasma. It works by inhibiting tyrosinase, allowing for the gradual lightening of brown spots. However, its use is regulated due to possible side effects, including irritation, redness, or allergic reactions. The idea of combining glycolic acid with hydroquinone might seem appropriate: the exfoliating action of the AHA could theoretically improve the penetration of hydroquinone and enhance its depigmenting efficacy.

However, the study previously mentioned in the hyaluronic acid section showed that the combination of hydroquinone and glycolic acid did not offer any greater benefit than hydroquinone alone. Not only was the improvement in the MASI score not more pronounced, but participants exposed to this combination also reported more adverse effects.

Thus, even though the combination of glycolic acid and hydroquinone may look appealing on paper, it is not necessarily appropriate. In Europe, hydroquinone is furthermore authorized only for professional use.

The alpha-arbutin, also called arbutin acid, is a natural hydroquinone derivative recognized for its mild and better tolerated brightening action. It works by inhibiting tyrosinase activity, thereby limiting the production of melanin responsible for pigmentation spots. Unlike hydroquinone, it is considered safer for cosmetic use, making it a popular ingredient in treatments aimed at evening out skin tone. Combining alpha-arbutin with glycolic acid could theoretically enhance their respective efficacies: by exfoliating the superficial layers of the epidermis, glycolic acid would facilitate the penetration of alpha-arbutin, optimizing its depigmenting action.

However, to date, no scientific study has evaluated the combination of glycolic acid and arbutin acid. Therefore, the potential benefits remain hypothetical.

Mandelic acid is an AHA prized for its mildness and good skin tolerance. Its large molecular size limits its penetration into the skin, making it an interesting choice for sensitive skin. Mandelic acid is often used to reduce pigmentation spots, with a gradual exfoliating effect that is less irritating than that of other AHAs. Combining mandelic acid with glycolic acid could theoretically allow one to benefit both from the deep, rapid action of the latter and the slower effect of mandelic acid, resulting in more balanced exfoliation.

A pilot study was conducted on 12 volunteers with acne. Once a week for six weeks, participants applied an exfoliating gel combining several acids: 16% glycolic acid, 8% lactic acid, 5% mandelic acid, 1% citric acid, 7% gluconolactone (a PHA), and 2% salicylic acid. Each session lasted 10 minutes, avoiding the eye and lip areas. The results showed a visible improvement in acne as early as the third week and a reduction in scarring after four weeks, with no notable side effects in any of the participants. However, even though these results appear promising, it remains difficult to draw precise conclusions about the specific synergy between glycolic acid and mandelic acid, since the tested treatment contained numerous other exfoliants.

The study nonetheless confirms that glycolic acid and mandelic acid are not incompatible and can be used together.

The kojic acid is a fungal-derived active ingredient renowned for its lightening properties, primarily used to reduce hyperpigmentation. It acts by inhibiting tyrosinase, thereby evening out skin tone and diminishing the appearance of brown spots. Pairing kojic acid with glycolic acid may offer a dual advantage: glycolic acid exfoliates the stratum corneum and promotes cell renewal, which enhances the penetration and efficacy of kojic acid, thus optimizing the result on hyperpigmentation.

A study evaluated the impact of adding 2% kojic acid to a gel already containing 10% glycolic acid and 2% hydroquinone in 40 women with melasma. Each patient applied the kojic acid–containing gel twice daily to one half of her face and the same formulation without kojic acid to the other half. After twelve weeks, both sides showed improvement, but the half treated with kojic acid produced superior results: 60% saw more than half of their melasma disappear, compared to 47.5% on the other side. Two patients achieved complete clearance of spots on the kojic acid–treated side. Redness and stinging were observed on both sides but resolved by week three. The researchers concluded that adding kojic acid enhances the effectiveness of glycolic acid.

It is advisable to remain cautious with kojic acid, which is suspected of acting as an endocrine disruptor and of being allergenic, mutagenic, and carcinogenic.