3-O-Ethyl-L-ascorbic acid: properties, uses, pros, cons, safety

3-O-Ethyl-L-ascorbic acid (3-O-Ethyl ascorbic acid) is a stable, water-soluble derivative of vitamin C (ascorbic acid) that is commonly used in skincare products for its brightening, antioxidant, and anti-aging properties. It is valued for its ability to penetrate the skin more effectively than traditional vitamin C, delivering its benefits deep into the skin. This ingredient helps reduce hyperpigmentation, boost collagen production, and protect the skin from environmental damage caused by free radicals.

Chemical Composition and Structure
3-O-Ethyl ascorbic acid is an etherified form of ascorbic acid, with an ethyl group attached to the third carbon of the ascorbic acid molecule. This modification enhances its stability compared to regular vitamin C, which is prone to oxidation. The chemical structure allows it to maintain its effectiveness for longer periods, making it ideal for use in formulations that require a stable form of vitamin C.

Physical Properties
3-O-Ethyl ascorbic acid typically appears as a white to off-white powder. It is water-soluble and easily incorporated into aqueous-based skincare formulations such as serums, creams, and lotions. Due to its improved stability, it remains effective over time, even in the presence of air and light, which typically degrade other forms of vitamin C.

The name defines the structure of the molecule:

• 3-O-Ethyl refers to the ethyl group (a two-carbon chain) which is attached to the oxygen atom at the third position of the ascorbic acid molecule. The molecule is designed with an ethyl group attached, making it lipophilic (oil-soluble). This lipophilic nature allows it to be well-absorbed into the skin, ensuring deeper penetration and providing antioxidant protection at various skin depths.
• Ascorbic acid is the chemical name of vitamin C, a nutrient vital to health. It is known for its antioxidant properties and its role in collagen synthesis.

Description of raw materials used in production

• Ascorbic acid. Vitamin C, used as the core molecule of the compound.
• Ethyl alcohol. Used to ethylate ascorbic acid.
• Catalysts. Used to facilitate the ethylation reaction.

The synthesis process takes place in several stages:

• Preparation. The process begins with the preparation of ascorbic acid, which is commercially available.
• Esterification. Ascorbic acid reacts with ethanol in the presence of an acid catalyst, often sulfuric acid. The reaction is heated and starts the esterification process. This reaction causes the formation of 3-O-ethyl ascorbic acid.
• Separation. The reaction mixture is allowed to cool. 3-O-ethyl ascorbic acid will separate from the reaction mixture.
• Purification. 3-O-ethyl ascorbic acid is then purified. This typically involves distillation, where 3-O-ethyl ascorbic acid is heated and the vapors are collected and condensed. This process helps to remove any remaining impurities.
• Quality control. The final product is tested to ensure it meets the specifications required for use in cosmetics and personal care products. This includes checking its purity, color and smell.

What it is used for and where

Ascorbic acid 3-O-ethyl is a compound that combines an ethyl group with ascorbic acid. It is often used in skin care products for its ability to brighten the skin, reduce the appearance of dark spots and help with the production of collagen. It is more stable and can penetrate the skin more easily than pure vitamin C, making it a popular choice for skin care formulations.

Medical

Dermatology. Employed in topical treatments for its anti-spot properties and to promote collagen production, enhancing skin texture and elasticity.

Cosmetics

Using a stable form of vitamin C like 3-O-Ethyl Ascorbic Acid ensures that the active ingredient remains effective, providing the desired skin benefits for a longer duration after application.

Skin conditioning agent. It is the mainstay of topical skin treatment as it has the function of restoring, increasing or improving skin tolerance to external factors, including melanocyte tolerance. The most important function of the conditioning agent is to prevent skin dehydration, but the subject is rather complex and involves emollients and humectants that can be added in the formulation.

CAS 86404-04-8

Molecular Formula    C₈H₁₂O₆

Molecular Weight   204.178 g/mol

Commercial Applications

Cosmetics. 3-O-Ethyl Ascorbic Acid is a key ingredient in many skincare formulations, hailed for its antioxidant, brightening, and anti-aging properties. Found in serums, creams, and sun protection products.

Hair Products. Due to its antioxidant properties, it can be included in hair products to shield hair from free-radical damage.

Research. Given its stability, it's also used in research to study the effects of vitamin C on the skin without the rapid degradation associated with ascorbic acid.

Studies

The aim of the work was the evaluation of selected biological and physicochemical, applicative properties of ethylated ascorbic acid (AAE) compared to ascorbic acid (AA). The antioxidant activity of AAE is significant. However, the reaction with 2,2-diphenyl-1-picrylhydrazyl (DPPH) indicates prolonged activity compared to AA. Variability in the antimicrobial activity of AAE may find practical application in the pharmaceutical and cosmetic industries. The potential for applicative aims may be supported by the relatively low in vitro toxicity of AAE (1).

3-O-ethyl ascorbic acid may be a good whitening ingredient in cosmetics. However, before it can be successfully used in cosmetics, its biofunctionality and stability need to be comprehensively investigated.  The reduction and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging ability of this compound were analyzed to assess its antioxidant potential. In addition, the tyrosinase inhibitory ability was analyzed to show the whitening capacity of 3-O-ethyl ascorbic acid (2).

Safety

Some cases of allergy have been reported:

Romita P, Foti C, Barlusconi C, Mercurio S, Hansel K, Stingeni L. Allergic contact dermatitis to 3-O-ethyl-L-ascorbic acid: An underrated allergen in cosmetics? Contact Dermatitis. 2020 Jul;83(1):63-64. doi: 10.1111/cod.13528.

Victoria-Martínez AM, Mercader-García P. Allergic Contact Dermatitis to 3-o-Ethyl-L-Ascorbic Acid in Skin-lightening Cosmetics. Dermatitis. 2017 Jan/Feb;28(1):89. doi: 10.1097/DER.0000000000000260.

Mamodaly M, Dereure O, Raison-Peyron N. A new case of allergic contact dermatitis caused by 3-o-ethyl ascorbic acid in facial antiageing cosmetics. Contact Dermatitis. 2019 Oct;81(4):315-316. doi: 10.1111/cod.13307.

References________________________________________________________________

(1) Golonka I, Oleksy M, Junka A, Matera-Witkiewicz A, Bartoszewicz M, Musiał W. Selected Physicochemical and Biological Properties of Ethyl Ascorbic Acid Compared to Ascorbic Acid. Biol Pharm Bull. 2017;40(8):1199-1206. doi: 10.1248/bpb.b16-00967. 

Abstract. The aim of the work was the evaluation of selected biological and physicochemical, applicative properties of ethylated ascorbic acid (AAE) compared to ascorbic acid (AA). Thermogravimetry (TG), differential thermogravimetry (DTG), and differential thermal analysis (DTA) were conducted, followed by the evaluation of AAE decomposition by the UV-Vis spectroscopic method including the influence of temperature and pH. Scavenging, antimicrobial activity and cytotoxicity against L929 fibroblasts were also performed. The difference in mass loss between AA and AAE was 30% via TG. DTA revealed characteristic exothermic and endothermic effects. The AAE solution was more thermally stable than AA. The calculated zero-order rate constants of free-radical scavenging kinetics for AAE were in the range of 4.9×10-3-1.35×10-2 s-1. The activation energy for the process was 11,2281 kJ/mol. AAE was active against Staphylococcus (S.) aureus and Enterococcus (E.) faecalis and acted stronger against Candida (C.) albicans than AA. The concentrations of AA ≥2.5% were cytotoxic, whereas in the case of AAE, a 10% concentration was considered cytotoxic. DTG enables the detailed differentiation between AA and AAE. AAE in aqueous solution is more stable compared to AA. The antioxidant activity of AAE is significant. However, the reaction with 2,2-diphenyl-1-picrylhydrazyl (DPPH) indicates prolonged activity compared to AA. Variability in the antimicrobial activity of AAE may find practical application in the pharmaceutical and cosmetic industries. The potential for applicative aims may be supported by the relatively low in vitro toxicity of AAE.

(2) Liao WC, Huang YT, Lu LP, Huang WY. Antioxidant Ability and Stability Studies of 3-O-Ethyl Ascorbic Acid, a Cosmetic Tyrosinase Inhibitor. J Cosmet Sci. 2018 Jul/Aug;69(4):233-243. 

Abstract. 3-O-ethyl ascorbic acid may be a good whitening ingredient in cosmetics. However, before it can be successfully used in cosmetics, its biofunctionality and stability need to be comprehensively investigated. The reduction and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging ability of this compound were analyzed to assess its antioxidant potential. In addition, the tyrosinase inhibitory ability was analyzed to show the whitening capacity of 3-O-ethyl ascorbic acid. Response surface methodology (RSM) was used to determine the optimal conditions for the ascorbic acid derivative in cosmetics. Based on the DPPH radical scavenging ability results, the half-inhibitory concentration (IC50) value of 3-O-ethyl ascorbic acid was 0.032 g/L. It also showed a good reducing ability at 1.5 g/L concentration. Based on the tyrosinase inhibition analysis, the IC50 value was 7.5 g/L. The optimal conditions to achieve the best stability were determined from the RSM as 36.3°C and pH 5.46.

More studies

Iliopoulos F, Sil BC, Moore DJ, Lucas RA, Lane ME. 3-O-ethyl-l-ascorbic acid: Characterisation and investigation of single solvent systems for delivery to the skin. Int J Pharm X. 2019 Jul 19;1:100025. doi: 10.1016/j.ijpx.2019.100025.

Tai A, Aburada M, Ito H. A simple efficient synthesis and biological evaluation of 3-O-ethylascorbic acid. Biosci Biotechnol Biochem. 2014;78(12):1984-7. doi: 10.1080/09168451.2014.946396. 

Li Y, Dong C, Cun D, Liu J, Xiang R, Fang L. Lamellar Liquid Crystal Improves the Skin Retention of 3-O-Ethyl-Ascorbic Acid and Potassium 4-Methoxysalicylate In Vitro and In Vivo for Topical Preparation. AAPS PharmSciTech. 2016 Jun;17(3):767-77. doi: 10.1208/s12249-015-0353-6.

Shimizu R, Yagi M, Kikuchi A. Suppression of riboflavin-sensitized singlet oxygen generation by l-ascorbic acid, 3-O-ethyl-l-ascorbic acid and Trolox. J Photochem Photobiol B. 2019 Feb;191:116-122. doi: 10.1016/j.jphotobiol.2018.12.012.