What is 3‐O‐Ethyl Ascorbic Acid and what is it used for?

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

Unlike pure ascorbic acid, which degrades rapidly in aqueous environments 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 biological effects similar 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, favorable skin affinity, and diverse biological effects.

Like ascorbic acid, 3-O-Ethyl Ascorbic Acid exhibits a strong antioxidant activity, enabling it to neutralize free radicals generated primarily by UV radiation, pollution, or environmental stress. By limiting the oxidation of lipids, proteins, and cellular DNA, it helps preserve the integrity of skin components and slow premature aging.

A study in vitro conducted on human keratinocytes (HaCaT) evaluated the photoprotective effect of 30% 3-O-ethyl ascorbic acid combined with lactic acid. After pre-treating the cells (5 mg/mL), they were exposed to 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.

3-O-Ethyl Ascorbic Acid is also used for its role in supporting the extracellular matrix. Similar to vitamin C, it plays a role in regulating collagen synthesis, a structural protein essential for skin firmness and mechanical resilience. By stimulating fibroblast activity and limiting dermal fiber degradation, it contributes to improved skin elasticity and reduced visibility of wrinkles and fine lines. In the same study cited 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 tenfold.

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

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

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

The allergological assessment carried out after recovery confirmed a positive reaction to the cosmetic product, followed by a strongly positive reaction to 3-O-Ethyl Ascorbic Acid at 5% in petrolatum, whereas tests on 20 other volunteers were negative. This outcome supports the hypothesis of an individual sensitization rather than a systematic allergenic potential of the active ingredient. It is also noteworthy that the patient perfectly tolerated the oral administration of vitamin C, confirming that the reaction is specific to cutaneous exposure and does not necessarily apply to 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 in tolerance tests. 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 specific reactivity. Even when an ingredient has an excellent safety profile, an individual reaction remains possible. That is why it is advisable to systematically perform a patch test beforehand when using a new cosmetic product for the first time.

• 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).