What is “3-O-Ethyl Ascorbic Acid” and what is its purpose?

3-O-Ethyl Ascorbic Acid is an ethylated derivative of vitamin C (ascorbic acid), developed to overcome the well-known limitations of the latter in cosmetics, notably its chemical instability and sensitivity to oxidation. At the molecular level, it is an ascorbic acid in which the hydroxyl group at position 3 has been modified by the addition of an ethyl group. This structural change gives the molecule improved stability against light, oxygen and heat, while preserving its biologically active ascorbic core.

Unlike pure ascorbic acid, which degrades rapidly in an aqueous environment and requires very stringent formulation conditions (acidic pH, protection from air and light), 3-O-Ethyl Ascorbic Acid is more stable. Once applied to the skin, it is gradually released and converted into active ascorbic acid by skin enzymes, allowing it to exert similar biological effects to those of vitamin C, while limiting the irritation sometimes observed with the pure form.

3-O-Ethyl Ascorbic Acid is one of the most widely used vitamin C derivatives in cosmetics, owing to its high stability, excellent skin affinity and the diversity of its biological effects.

Like ascorbic acid, 3-O-Ethyl Ascorbic Acid possesses a pronounced antioxidant activity, enabling it to neutralise free radicals generated notably by exposure to UV radiation, pollution or environmental stress. By limiting the oxidation of lipids, proteins and cellular DNA, it helps to preserve the integrity of skin components and to slow down premature ageing.

A study in vitro conducted on human keratinocytes (HaCaT) assessed the photoprotective effect of 3-O-Ethyl Ascorbic Acid (30%), combined with lactic acid. After pre-treating the cells (5 mg/mL), they were exposed to a controlled UVB irradiation (2.5 mJ/cm²), sufficient to induce DNA damage. The results show a significant reduction in γ-H2AX protein expression, a key marker of DNA double-strand breaks, indicating a protective effect of 3-O-Ethyl Ascorbic Acid against UV-induced genomic damage.

The 3-O-Ethyl Ascorbic Acid is also utilised for its role in the support of the extracellular matrix. As with vitamin C, it is involved in the regulation of collagen synthesis, a structural protein essential for skin firmness and mechanical strength. By stimulating fibroblast activity and limiting the degradation of dermal fibres, it contributes to improved skin elasticity and reduced visibility of wrinkles and fine lines. In the same study mentioned above, the activity of 3-O-Ethyl Ascorbic Acid was evaluated on normal human dermal fibroblasts (NHDF). After 24 hours of pre-treatment, a marked increase in collagen synthesis was observed, exceeding that of untreated cells by a factor of ten.

Moreover, one of the principal advantages of 3-O-Ethyl Ascorbic Acid lies in its brightening and evening-out effect. It works on skin pigmentation by modulating tyrosinase activity, a key enzyme in melanogenesis, and by influencing the signalling pathways involved in melanin production within melanocytes. The cited study also assessed the depigmenting effect on a reconstructed human pigmented epidermis (RHPE) model of a 30% 3-O-Ethyl Ascorbic Acid serum, following repeated application over four days. The results show a significant reduction in melanin content, without adversely affecting tissue viability, demonstrating effective regulation of melanogenesis.

Overall, 3-O-Ethyl Ascorbic Acid exhibits a favourable safety profile, particularly at concentrations commonly used in cosmetics.

Most of the available data indicate safe use, with no notable adverse effects. Nevertheless, as with many biologically active agents, of rare cases of contact dermatitis have been reported in the literature. A detailed case report describes a 42-year-old woman with no atopic background who developed pruritic eczematous lesions accompanied by oedema. The symptoms appeared a few days after the third application of an antioxidant concentrate containing 3-O-Ethyl Ascorbic Acid. Discontinuation of the product led to complete resolution of the lesions within two weeks.

Allergological investigations conducted after recovery confirmed a positive reaction to the cosmetic product, followed by a strongly positive reaction to 3-O-Ethyl Ascorbic Acid tested at 5% in petroleum jelly, whereas tests carried out on 20 other volunteers were negative. This result supports the hypothesis of an individual sensitisation rather than a systematic allergenic potential of the active ingredient. It is also interesting to note that the patient perfectly tolerated oral intake of vitamin C, confirming that the reaction is specific to cutaneous exposure and does not necessarily concern other forms or routes of administration.

Since 2014, only four isolated cases of allergic contact dermatitis attributable to 3-O-Ethyl Ascorbic Acid have been reported, with reactions generally mild to moderate during tolerance testing. On a global scale and given its increasing use, these data suggest that the allergic risk is rare but present.

In practice, this reminds us that each skin type has its own inherent reactivity. Even when an ingredient has an excellent safety profile, an individual reaction is still possible. That is why it is advisable to systematically carry out a patch test in advance when first using a new cosmetic product.

• LANE M. E. & al. 3-O-ethyl-L-ascorbic acid: Characterisation and investigation of single solvent systems for delivery to the skin. International Journal of Pharmaceutics (2019).

• STINGENI L. & al. Allergic contact dermatitis to 3-O-ethyl-L-ascorbic acid: An underrated allergen in cosmetics? Contact Dermatitis (2020).

• MOCCHI R. & al. The anti-ageing and whitening potential of a cosmetic serum containing 3-O-ethyl-L-ascorbic acid. Life (2021).

• YANG H.-L. & al. The anti-melanogenic effects of 3-O-ethyl ascorbic acid via Nrf2-mediated α-MSH inhibition in UVA-irradiated keratinocytes and autophagy induction in melanocytes. Free Radical Biology and Medicine (2021).

• LEONARDI G. R. & al. Cosmetics formulations containing vitamin C and the instability challenge. Research Journal of Topical and Cosmetic Sciences (2022).