Which active ingredients can glycolic acid be combined with?

The niacinamide is a versatile active ingredient that soothes redness, diminishes pigment spots by limiting melanin transfer to keratinocytes, and fortifies the skin barrier by stimulating ceramide synthesis. When combined with glycolic acid, it counteracts the sensitivity sometimes induced by this AHA while enhancing its efficacy.

A two-month prospective study involving 25 women with mild acne confirmed the value of this synergistic approach. After eight weeks of daily application of a gel containing both active ingredients, results demonstrated an almost 80% reduction in acne lesions, corroborated by a significant improvement in the Global Acne Grading System (GAGS) clinical score used to assess acne severity. A decrease in inflammation and pigmentary disturbances was also observed, while the skin barrier function remained intact, indicating good tolerability.

Although this combination works within the same formulation, it is not advisable to layer two distinct products. Glycolic acid requires an acidic pH (3 - 4) to be effective, and applying a niacinamide serum (pH 5 - 7) can reduce its exfoliating action.

The combination of glycolic acid with retinoids is based on the complementarity of their mechanisms of action. Retinoids (retinol, retinal, retinoic acid, etc.) are renowned for their ability to normalise cell turnover, reduce inflammation and stimulate collagen synthesis, thereby contributing to the reduction of blemishes and acne scarring. Combined with the keratolytic properties of theglycolic acid, they provide a particularly beneficial synergy for acne-prone skin or skin exhibiting pigment irregularities.

A twelve-week clinical study involving 35 patients aged 17 to 34 years assessed the efficacy of a combination of glycolic acid (12%) and retinoic acid (0.025%). The results revealed a significant improvement in scarring in 91.4% of participants, confirming the efficacy of this combination and its potential as an alternative to more invasive treatments.

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

The vitamin C (ascorbic acid) is recognised for its antioxidant and brightening properties: it neutralises free radicals responsible for oxidative stress and inhibits tyrosinase activity, thus limiting melanin synthesis. When combined with glycolic acid, whose exfoliating action promotes the penetration of active ingredients, vitamin C’s efficacy is enhanced, notably in reducing hyperpigmentation.

A clinical study involving 178 patients with melasma (MASI score > 10) compared two protocols: a 40% glycolic acid peel every two weeks combined with daily application of a vitamin C cream, and a standard treatment comprising 4% hydroquinone, tretinoin and corticosteroids. After six weeks, 94.4% of patients in the glycolic acid + vitamin C group demonstrated a significant improvement in hyperpigmentation, versus 79.8% in the control group, confirming the potential of this combination as an effective and better-tolerated alternative to conventional depigmenting treatments.

The combination of glycolic acid and pure vitamin C may be overly irritating for sensitive skin.

Thehyaluronic acid is renowned for its moisturising properties, capable of retaining up to 1,000 times its weight in water depending on its molecular weight. As a key active ingredient in cosmetics, it helps to restore the skin’s barrier function and limit water loss, providing comfort and suppleness. When associated with glycolic acid, it alleviates any sensation of tightness and reduces the risk of intolerance, without compromising the latter’s exfoliating effect.

A clinical study conducted on 100 patients with melasma compared various combinations of depigmenting agents: hydroquinone alone (group 1), hydroquinone + glycolic acid (group 2), hydroquinone + hyaluronic acid (group 3), hydroquinone + glycolic acid + hyaluronic acid (group 4), and placebo (group 5). After 12 weeks, all hydroquinone-containing groups showed an improvement in MASI score reflecting a reduction in hyperpigmentation, whilst the addition of hyaluronic acid has reduced the frequency and severity of glycolic acid-related adverse effects, improving its tolerability.

The combination of glycolic acid with salicylic acid is based on the principle of combining two complementary exfoliants. Thesalicylic acid (BHA), lipid-soluble, penetrates the pores and unblocks comedones, while glycolic acid acts on the surface to exfoliate the epidermis. This combination enables more thorough cleansing and optimises blemish reduction.

A study involving 66 patients with mild to moderate inflammatory acne evaluated a serum containing these two acids, applied each evening over a two-week period. Over 90% of participants reported a notable improvement in acne, with a reduction in comedones and cystic lesions, and 70–80% reported less oily, more uniform skin.

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

Theazelaic acid is a dicarboxylic acid with anti-inflammatory, antibacterial and depigmenting properties. It reduces the proliferation of Cutibacterium acnes, soothes the skin and acts on hyperpigmentation by inhibiting tyrosinase. When combined with glycolic acid, it contributes to a smoother, more even complexion.

A study of 70 patients with acne compared a 20% azelaic acid cream plus a 15% glycolic acid lotion with a 0.025% tretinoin solution, applied twice daily for 12 weeks. The azelaic acid/glycolic acid combination significantly reduced acne lesions, with efficacy comparable to tretinoin for non-inflammatory lesions and superior for inflammatory lesions, while offering better tolerability (less dryness, redness and scaling).

The bakuchiol is a plant-derived active ingredient often presented as a gentle alternative to retinol. It acts on cellular renewal, stimulates collagen synthesis and has antioxidant and anti-inflammatory properties. It thus helps to improve the appearance of fine lines, uneven skin texture and pigmented spots.

When combined with glycolic acid, bakuchiol could potentiate the effects of exfoliation and cellular renewal without increasing the risk of irritation often encountered with this AHA. This combination thus appears promising for smoothing the skin and evening out the complexion.

Even if combining glycolic acid and bakuchiol seems theoretically promising, no clinical study has yet assessed the efficacy or tolerability of this combination.

Thealpha-arbutin is a natural derivative of hydroquinone, recognised for its gentle, better-tolerated lightening action. It works by inhibiting tyrosinase activity, thereby reducing the production of melanin responsible for brown spots. Unlike hydroquinone, it is considered safer for cosmetic use, making it a popular ingredient in treatments aimed at evening out the complexion. Combining 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 effect.

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

Combining glycolic acid with lactic acid or mandelic acid may appear redundant, as all three belong to the family of alpha-hydroxy acids (AHAs). However, they act complementarily to refine skin texture whilst limiting the risk of irritation, thus forming interesting synergies.

Combined withlactic acid, glycolic acid benefits from its milder action and moisture-retaining properties, which support hydration while enhancing cellular cohesion. This complementary effect was investigated in a clinical study assessing the efficacy of a peel combining 2% glycolic acid and 2% lactic acid, applied to the facial skin of 23 women with acne-prone skin. The results demonstrated a significant reduction in open and closed comedones as early as the first week, with only two participants experiencing transient irritation.

Themandelic acid also constitutes a relevant combination. Its relatively high molecular weight limits skin penetration, providing a gradual, well-tolerated effect particularly suited to sensitive skin. A pilot study using a multi-acid gel (including 16% glycolic acid, 8% lactic acid and 5% mandelic acid, among others) demonstrated an improvement in acne by the third week and a reduction in scarring after four weeks, with no notable side effects. Although it remains challenging to draw precise conclusions about the specific synergy between glycolic and mandelic acids due to the presence of other exfoliants, the study confirms their compatibility.

Ultimately, combining glycolic acid with other AHAs allows for modulation of exfoliation intensity according to skin needs : the rapid and profound action of glycolic acid is balanced by the gentler, hydrating and progressive effects of lactic acid and mandelic acid. These combinations offer a nuanced approach to chemical exfoliation, adaptable to various skin types and tolerance levels.

The glycerine is one of the most widely used humectants in cosmetics, renowned 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" action. It forms a film on the epidermal surface that reduces water loss. In formulations, glycerine often plays a protective role and is frequently used to counterbalance the irritating effects of certain active ingredients, such as glycolic acid, thereby ensuring better tolerance.

The combination of glycerine and glycolic acid is widespread in cosmetic formulations as it helps to mitigate the side effects associated with glycolic acid while preserving its exfoliating efficacy.

The kojic acid, of fungal origin, is known for its ability to reduce the appearance of brown spots and even out skin tone. Paired with glycolic acid, which exfoliates the stratum corneum and promotes cell renewal, its efficacy is enhanced. A study involving 40 women with melasma compared the application of a gel containing 10% glycolic acid and 2% hydroquinone, with or without 2% kojic acid, on each side of the face, twice daily for 12 weeks. Improvement was observed on both sides, but the side treated with kojic acid showed superior results: 60% of patients saw more than half of their melasma resolve, compared to 47.5% on the other side, with two cases of complete clearance. Side effects (redness, tingling) were transient and had resolved by the third week. The study concluded that the addition of kojic acid could bolster the efficacy of glycolic acid.

Caution should be exercised with kojic acid, which is suspected of acting as an endocrine disruptor and of being allergenic, mutagenic and carcinogenic.

The benzoyl peroxide is an essential agent in acne management due to its antibacterial properties, particularly effective against Cutibacterium acnes, the bacterium involved in the worsening of acne. It also possesses an exfoliating effect and helps reduce skin inflammation.

Combining benzoyl peroxide and glycolic acid could theoretically be relevant for reducing blemishes, whether they are comedones or inflammatory lesions (papules and pustules). However, no study has focused on the combination of glycolic acid and benzoyl peroxide, and the irritating potential of these two agents remains a significant limitation.

We advise against using glycolic acid products and benzoyl peroxide products together, as this may irritate your skin.

Hydroquinone is a reference depigmenting agent, acting by inhibiting tyrosinase to gradually lighten dark spots. However, its use remains regulated due to potential side effects, including irritations, redness, or allergic reactions. Combining it with glycolic acid, which could theoretically enhance its penetration, does not appear to offer any additional benefit: a study showed that the combination did not further improve the MASI score compared to hydroquinone alone, while increasing the frequency of adverse effects.

Thus, even if the combination of glycolic acid and hydroquinone may seem appealing on paper, it is not necessarily relevant. In Europe, hydroquinone is, in fact, only permitted for professional use.

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• FARAG S. E. & al. Assessment of the effectiveness and safety of combining hydroquinone, glycolic acid, and hyaluronic acid in the treatment of melasma. Journal of Cosmetic Dermatology (2015).

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• ASLAM K. & al. Effectiveness of 40% glycolic acid peel and topical vitamin C cream compared to a triple combination cream in the treatment of epidermal melasma. Khyber Journal of Medical Sciences (2023).