Some skincare actives complement each other and work in synergy. Others should not be combined to avoid skin irritation or reduced efficacy. Which actives should you avoid mixing? Discover them in this article.

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- Active Ingredients
- Which combinations of active ingredients should be avoided?
Which combinations of active ingredients should be avoided?
- Combination to avoid No. 1: multiple exfoliants (AHAs, BHAs, retinol)
- Combination to avoid No. 2: exfoliants (AHAs, BHAs, retinol…) and pure vitamin C
- Combination to avoid No. 3: retinol and benzoyl peroxide?
- Combination to avoid No. 4: dihydroxyacetone (DHA) and peptides?
- Sources
Combination to avoid No. 1: multiple exfoliants (AHAs, BHAs, retinol).
The simultaneous application of multiple exfoliants, such as AHAs (alpha-hydroxy acids, such as glycolic acid or lactic acid), the BHAs (beta-hydroxy acids, such as salicylic acid), or retinol, is not recommended for sensitive skin. Exfoliants work by breaking the bonds between corneocytes, promoting the removal of stratum corneum cells and improving skin texture. When combined, their keratolytic effect is additive and can compromise the skin barrier, leading to redness, tingling, dryness, and peeling.
Despite this, context is important. Combining exfoliating agents can be useful, as certain studies have shown. A clinical study of 90 patients with melasma demonstrated that a peel containing 35% of glycolic acid or a peel combining 20% of salicylic acid and 10% of mandelic acid was effective in reducing hyperpigmentation. After applications every two weeks for a twelve-week period, the MASI (Melasma Area and Severity Index), measuring melasma severity, decreased by 62.36% in the glycolic acid group and by 60.98% in the salicylic/mandelic acid group. However, despite this efficacy, numerous side effects were reported, including redness and burning sensations.

In another study, a serum combining glycolic acid and salicylic acid was evaluated in 66 patients with inflammatory or cystic acne. After two weeks of once-daily use, more than 90% of patients reported a reduction in acne, improved skin texture and decreased sebum production. However, the authors did not specify the concentrations used or detail any observed side effects, which limits the interpretation of the results.
Combining exfoliating actives can provide clinical benefit, but daily use is not recommended, especially for sensitive skin. To minimise the risk of irritation, alternate applications every second evening rather than using them together.
Combination to avoid No. 2: exfoliants (AHAs, BHAs, retinol…) and pure vitamin C.
Combining exfoliants such as AHAs or BHAs with pure vitamin C can cause irritation in sensitive skin. As a reminder, the vitamin C pure form (INCI: Ascorbic Acid) has an acidic nature with a pH below 3.5. This low pH is necessary to ensure its stability and antioxidant activity. It can weaken the skin barrier and cause redness and stinging. That is why some formulations include derivatives of vitamin C, which are less irritating. When used simultaneously with exfoliating agents, pure vitamin C enhances their keratolytic action and increases skin sensitivity.
However, as with simultaneous exfoliant use, combining vitamin C with exfoliants may be beneficial for reducing wrinkles and pigmentation spots. In a study conducted in Singapore with 15 patients showing signs of photoageing, 70% glycolic acid peels combined with vitamin C—at an undisclosed concentration—were applied three times, at four-week intervals. After twelve weeks, a visible improvement in skin texture and radiance was observed. However, common side effects, such as redness and swelling, were reported by several patients and persisted for weeks after the final treatment. These side effects were assessed on a scale from 1 to 4: (1) no side effects, (2) mild, (3) moderate, and (4) severe.
Side effect | Week 4 | Week 12 | Week 162.38 ± 0.83 |
---|---|---|---|
Redness | 2.38 ± 0.83 | … 2,23 ± 0,49 | 1,15 ± 0,36 |
Swelling | … 2,08 ± 0,83 | 1,38 ± 0,49 | 1 ± 0.00 |
Another study by NATAKANKITKUL and colleagues compared three formulations: one with 0.2% retinol, one with 5% sodium ascorbyl phosphate, a vitamin C derivative, and one combining both. Among 45 participants with acne, those using the combined formula showed a greater reduction in acne lesions after eight weeks. However, irritation was reported, although frequency and severity were not detailed. This suggests that when combined with retinol, even milder vitamin C derivatives may not be tolerated by sensitive skin.

Pure vitamin C and exfoliants can, in theory, be combined to prevent photoageing or reduce blemishes. However, this combination can irritate sensitive skin.
Combination to avoid No. 3: retinol and benzoyl peroxide?
The retinol and the benzoyl peroxide are two agents used in acne management. Each has a distinct mechanism of action. retinol promotes cell turnover and normalises keratinisation, which prevents pore blockage. By contrast, benzoyl peroxide targets the bacterium Cutibacterium acnes, the bacterium involved in the formation of inflammatory lesions, while also exerting a mild keratolytic effect. However, some suggest that retinol and benzoyl peroxide should not be combined because they may interact: benzoyl peroxide, as an oxidising agent, may oxidise retinol, reducing its effectiveness and increasing the risk of irritation.
Despite these warnings, recent data suggest that in well-calibrated formulations the retinol–benzoyl peroxide pairing can improve mild acne. A clinical study evaluated a cream combining 4% benzoyl peroxide, 0.05% retinol, 0.5% retinyl palmitate, 1% mandelic acid and glycyrrhetinic acid. Over 12 weeks, 20 patients with mild acne applied the cream once a day to their face. The results showed a good overall tolerance, with limited, transient irritation. In addition, there was a mean reduction of 65% in comedones, 62% in papular lesions and 80% in pustular lesions.
It appears that, when properly dosed, the combination of retinol and benzoyl peroxide offers an effective option for managing mild acne. However, as a precaution, it is advisable to introduce these actives in stages, for example by applying them on alternate nights at first.
Combination to avoid No. 4: dihydroxyacetone (DHA) and peptides?
Dihydroxyacetone (DHA) is the most used active ingredient in self-tanning products. Its mechanism relies on the Maillard reaction, during which DHA reacts with free amine groups on proteins in the stratum corneum, particularly arginine residues, forming brown pigments called melanoidins that give skin a tan. Formulations include peptides. These short amino acid chains stimulate collagen synthesis and reduce wrinkles. Peptides contain free amine groups.
One can therefore assume that the DHA reacts with peptides similar to its interaction with stratum corneum proteins. It may alter peptide structure, reducing efficacy or rendering peptides inactive. DHA would react less with skin proteins, decreasing its self-tanning effect. These remain hypotheses based on the potential chemical reactivity of these molecules. To date, no study has confirmed this interaction, but it remains a point of caution in formulation. Thus, to avoid compromising the efficacy of your self-tanner and peptide treatment, we recommend not applying them at the same time.
Sources
FOURTANIER A. & al. Histological evaluation of a topically applied retinol-vitamin C combination. Skin Pharmacology and Physiology (2005).
NATAKANKITKUL S. & al. Comparison of clinical efficacies of sodium ascorbyl phosphate, retinol and their combination in acne treatment. International Journal of Cosmetic Science (2009).
GUPTA C. & al. Comparative evaluation of efficacy and tolerability of glycolic acid, salicylic mandelic acid, and phytic acid combination peels in melasma. Dermatologic Surgery (2016).
CIRIMINNA R. & al. Dihydroxyacetone: An updated insight into an important bioproduct. ChemistryOpen (2018).
CAMPIONE E. & al. Clinical evidence on the efficacy and tolerability of a topical medical device containing benzoylperoxide 4%, retinol 0.5%, mandelic acid 1% and lactobionic acid 1% in the treatment of mild facial acne: an open label pilot study. Clinical, Cosmetic and Investigational Dermatology (2019).
HADDAD L. & al. Two is better than one: The combined effects of glycolic acid and salicylic acid on acne-related disorders. Journal of Cosmetic Dermatology (2020).
HO S.-A. & al. The efficacy and safety of a 70% glycolic acid peel with vitamin C for the treatment of photoaging. Journal of Surgical Dermatology (2021).
YORK J. P. & al. Real-world adverse events associated with encapsulated benzoyl peroxide/tretinoin, 3%/0.1%, and encapsulated benzoyl peroxide, 5%. Dermatology and Therapy (2024).
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