Which active ingredients should be combined with glycolic acid?

Combining the glycolic acid with lactic acid may seem redundant, since both belong to the alpha-hydroxy acid (AHA) family. However, they act in a complementary manner. The glycolic acid, the smallest AHA, penetrates rapidly and deeply into the epidermis, stimulating cell renewal and effectively exfoliating the superficial layers. The lactic acid, in contrast, works more gently, promoting skin hydration through its humectant properties while reinforcing cell cohesion. Together, glycolic acid and lactic acid enable skin exfoliation whilst minimising the risk of irritation, thus constituting an interesting synergy.

This complementarity was investigated in a clinical study evaluating the efficacy of a peel combining 2% glycolic acid and 2% lactic acid applied to the faces of 23 women with acne-prone skin. The participants were divided into two groups: one received the peel alone, while the other underwent the peel in combination with a physical pressure technique. The results showed a significant reduction in both blackheads and whiteheads from the first week in both groups, although the effect was more pronounced in those receiving the combined treatment. In terms of tolerability, two of the 23 volunteers experienced irritation, which subsided within thirty minutes.

Glycolic acid and lactic acid can refine the skin’s texture and target imperfections.

The combination of glycolic acid with salicylic acid is based on the principle of combining two complementary types of exfoliants. The salicylic acid, a beta-hydroxy acid (BHA), is distinguished by its solubility in sebum which allows it to penetrate the skin's pores and unclog them by dissolving sebum plugs and dead cells responsible for comedones. By combining salicylic acid with glycolic acid, which acts primarily at the surface, a more complete exfoliation of the epidermis and a thorough pore cleanse are achieved, thereby optimising the reduction of imperfections.

A study was conducted to evaluate the efficacy of a serum combining glycolic acid and salicylic acid. 66 patients with mild to moderate inflammatory acne applied this product each evening for two weeks. The results show that over 90% of participants observed a notable improvement in their acne, with a reduction in comedones and cystic lesions, while 70-80% reported less oily, more even skin.

Although highly effective against imperfections, this combination is not recommended for sensitive skin.

The combination of glycolic acid with the retinoids is based on the complementarity of their mechanisms of action. The retinoids, whether that be retinol, retinal or retinoic acid, are vitamin A derivatives renowned for their ability to normalise cell turnover, reduce inflammation and stimulate collagen synthesis, rendering them particularly effective at reducing blemishes and fading acne scars. By combining the keratolytic effects of glycolic acid with those of the retinoids, one achieves a valuable synergy for acne-prone skin or skin displaying pigmentary irregularities.

A twelve-week study evaluated the efficacy of the combination of glycolic acid (12%) and retinoic acid (0.025%) in 35 patients aged between 17 and 34 years with acne scarring. The results showed a significant improvement in scarring in 91.4% of the patients, demonstrating that this combination effectively reduces the appearance of acne scars and can minimise 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 help to improve the appearance of fine lines, skin texture irregularities and pigmentation spots. When combined with glycolic acid, bakuchiol could enhance the effects of exfoliation and cellular renewal without increasing the risk of irritation 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 appears intriguing from a theoretical standpoint, no clinical study has yet evaluated the efficacy or tolerability of this combination.

The benzoyl peroxide is a cornerstone active ingredient in acne management thanks to its antibacterial properties, which are particularly effective against Cutibacterium acnes, the bacterium implicated in the exacerbation of acne. It also exerts an exfoliating effect and helps to reduce skin inflammation. Combining benzoyl peroxide and glycolic acid could, in theory, be pertinent for reducing blemishes, whether open or closed comedones or inflammatory lesions (papules and pustules). However, no study has examined the combination of glycolic acid and benzoyl peroxide, and the irritant potential 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.

Azelaic acid 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 soothing the skin. Azelaic acid also has a recognised effect on post-inflammatory hyperpigmentation and melasma, thanks to its ability to inhibit tyrosinase, the enzyme responsible for converting tyrosine into melanin. Combined with glycolic acid, azelaic acid may help achieve a smoother, more even complexion.

Azelaic acid and glycolic acid may be beneficial for skin prone to blemishes and/or displaying pigmented 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 against those of a 0.025% tretinoin solution. The 12-week protocol involved two daily applications, morning and evening, with dermatological follow-up. The results demonstrate that the azelaic acid/glycolic acid combination significantly reduced the number of acne lesions, matching the efficacy of tretinoin for non-inflammatory lesions and exceeding it for inflammatory lesions. Furthermore, the tolerability proved superior, with patients experiencing less dryness, redness and flaking than with tretinoin.

Hyaluronic acid stands out for its exceptional hydrating properties. Depending on its molecular weight, it can retain up to 1,000 times its weight in water within the extracellular matrix. A key active ingredient in cosmetics, the hyaluronic acid helps to restore the barrier function and limit transepidermal water loss, providing comfort and suppleness to the skin. Its combination with glycolic acid, known for its exfoliating action and potential to irritate, is therefore of interest: hyaluronic acid enhances skin hydration, counteracting any feelings of tightness and reducing the risk of intolerance to glycolic acid, without compromising its exfoliating effects.

A clinical study conducted on 100 patients with melasma evaluated several combinations of depigmenting regimens. The participants were allocated into five groups: hydroquinone alone (group 1), hydroquinone with glycolic acid (group 2), hydroquinone combined with hyaluronic acid (group 3), hydroquinone plus glycolic and hyaluronic acids (group 4) and a placebo group. After 12 weeks of daily application, the groups receiving hydroquinone alone, or combined with hyaluronic acid or the glycolic/hyaluronic acid duo, showed a notable improvement in the MASI score, reflecting a reduction in hyperpigmentation. In parallel, the addition of hyaluronic acid reduced the frequency and severity of adverse effects observed with glycolic acid alone, suggesting that it improves the tolerability of this agent.

Glycerine is one of the humectants most widely used in cosmetics, recognised 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. Glycerine also has an occlusive effect. It forms a film on the epidermal surface that reduces water loss. In formulations, the glycerine often plays a protective role and is frequently used to counteract the irritating effects of certain actives, such as glycolic acid, thus ensuring better tolerance.

The combination of glycerine and glycolic acid is widely used in cosmetic formulations because it helps to minimise the side effects associated with glycolic acid while preserving its exfoliating efficacy.

The vitamin C, also known as ascorbic acid, is an active ingredient primarily recognised for its antioxidant and brightening properties. It neutralises free radicals involved in oxidative stress, while inhibiting tyrosinase activity and thus reducing melanin production. This makes vitamin C a preferred ingredient in the management of pigmentary spots and dull complexion. In synergy with glycolic acid, which aids the penetration of active compounds by removing dead cells from the skin’s surface, vitamin C’s effects can be magnified, especially in reducing hyperpigmentation.

A clinical study assessed this combination for the management of melasma. The trial involved 178 patients with marked hyperpigmentation (MASI score > 10), divided into two groups. The first group received a 40 % glycolic acid peel every two weeks, combined with a daily application of a vitamin C–based cream. The second group followed a standard protocol based on a 4 % hydroquinone cream combined with tretinoin and topical corticosteroids. After six weeks, results showed a significantly greater improvement in the glycolic acid + vitamin C group, with a reduction in hyperpigmentation in 94.38 % of participants, versus 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 may be overly 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 acts by calming redness and limiting the transfer of melanin to keratinocytes, which helps to fade hyperpigmentation. Additionally, it strengthens the skin barrier by stimulating ceramide synthesis, making it an excellent ally for countering the sensitivity sometimes associated with exfoliating acids. In combination with glycolic acid, niacinamide therefore enhances both the efficacy and tolerability of this AHA.

A two-month prospective study of 25 women with mild acne confirmed the benefit of this synergy. Participants applied a gel daily containing, among other active ingredients, niacinamide and glycolic acid. After eight weeks, the results showed a near 80% reduction in the number of acne lesions and a significant improvement in the GAGS clinical score, which is used to assess acne severity. Analyses also revealed reductions in inflammation and pigmentary irregularities. Finally, measurements of transepidermal water loss indicated that the skin’s barrier function remained intact, highlighting good tolerability of the treatment despite the presence of an AHA.

Note : While some products are formulated to contain glycolic acid and niacinamide, it can sometimes be counterproductive to layer two products containing these actives. For instance, our glycolic acid exfoliating serum has a low pH of 3–4, whereas our niacinamide unifying serum has a higher pH around 5–7. If they are mixed, the niacinamide will raise the pH of the glycolic acid serum, reducing its efficacy.

The hydroquinone is considered a benchmark depigmenting agent and is used in the treatment of hyperpigmentation and melasma. It works by inhibiting tyrosinase, thereby gradually lightening brown spots. However, its use is regulated due to potential side effects, including irritation, redness or allergic reactions. The idea of combining glycolic acid with hydroquinone may seem relevant: the exfoliating action of the AHA could theoretically improve hydroquinone penetration and enhance its depigmenting efficacy.

Nevertheless, the study referred to earlier in the hyaluronic acid section demonstrated that the hydroquinone + glycolic acid combination did not confer any additional benefit over hydroquinone alone. Not only was the improvement in the MASI score not more pronounced, but participants exposed to this combination also reported a higher incidence of adverse effects.

Thus, even though the combination of glycolic acid and hydroquinone might appear attractive on paper, it is not necessarily relevant. In Europe, hydroquinone is, moreover, authorised solely for professional use.

The alpha-arbutin, also known as arbutic acid, is a natural derivative of hydroquinone recognised for its mild and better-tolerated brightening action. It acts by inhibiting tyrosinase activity, thereby limiting the production of melanin responsible for pigment spots. Unlike hydroquinone, it is regarded as 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, optimising its depigmenting action.

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

The mandelic acid is an AHA valued for its mildness and good skin tolerance. Its relatively large molecular size limits its penetration into the skin, making it an appealing choice for sensitive skin. Mandelic acid is often used to fade pigmented spots, with a gradual exfoliating effect that is less irritating than that of other AHAs. Combining mandelic acid with glycolic acid could theoretically offer both the deep, rapid action of the latter and the slower effect of mandelic acid, resulting in more balanced exfoliation.

A pilot study was carried out on 12 volunteers with acne. Once a week for six weeks, participants applied an exfoliating gel comprising several acids: 16% glycolic acid, 8% lactic acid, 5% mandelic acid, 1% citric acid, 7% gluconolactone (PHA) and 2% salicylic acid. Each application lasted 10 minutes, avoiding the eye and lip areas. The results demonstrated a visible improvement in acne from the third week and a reduction in scarring after four weeks, with no notable adverse effects reported by any of the participants. However, although these findings appear promising, it remains difficult to draw precise conclusions regarding the specific synergy between glycolic acid and mandelic acid, since the formulation tested contained multiple other exfoliating agents.

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

Kojic acid is a fungal-derived active recognised for its brightening properties, primarily used to reduce hyperpigmentation. It acts by inhibiting tyrosinase, which helps even out the complexion and diminish the appearance of brown spots. Pairing kojic acid with glycolic acid could provide a dual benefit: glycolic acid exfoliates the stratum corneum and promotes cell renewal, thereby improving the penetration and efficacy of kojic acid, thus optimising the outcome on hyperpigmentation.

A study assessed 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 to one half of her face and the same formulation without kojic acid to the other half twice daily. After twelve weeks, both sides showed improvement, but the half treated with kojic acid yielded superior results: 60% saw more than half of their melasma disappear, compared with 47.5% on the other side. Two patients achieved complete clearance of spots on the side treated with kojic acid. Side-effects such as redness and tingling were observed on both sides but had resolved by the third week. The researchers concluded that adding kojic acid enhances the efficacy of glycolic acid.

It is prudent to exercise caution with kojic acid, which is suspected of acting as an endocrine disruptor and of being allergenic, mutagenic and carcinogenic.

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