Vitamin C is the most common antioxidant in skin. Unfortunately, humans do not have the enzyme (L-gluconogamma lactone oxidase) to make vitamin C, therefore it must be obtained from external sources.

L’ascorbic acid is the active form of vitamin C that carries out the biologic effects. Besides retinoids, vitamin C is probably the next most studied ingredient in skincare. Ascorbic acid has many benefits. Repeat studies have shown it helps prevent photodamage from UVA and UVB radiation. It stimulates collagen production, serving as a co-factor for enzymes in collagen production. Lastly, vitamin C is a great lightening ingredient. It blocks tyrosinase, a key enzyme in melanin production.

However, vitamin C is highly unstable. It easily oxidizes in light, heat, pH change, and presence of other other ions. This has led to the development of various vitamin C derivatives that are more stable while trying to retain efficacy. However formulation continues to be a challenge. Demonstrating ingredient effectiveness needs to occur not just in the laboratory setting or on animals, it also needs assessment on human skin. Unfortunately, there’s a paucity of data regarding skincare ingredients in general (compared to medical dermatology), and some publications are conflicting. One study may show benefit of a derivative, while another demonstrates no efficacy. This inherently speaks to the challenges of manufacturing L-ascorbic acid, as formulation is everything.

Review of vitamin C and derivatives

L-ascorbic acid

Active form of vitamin C (AA). The most studied form of vitamin C in literature.

hydrophilic molecules

Optimal formulation:

pH: 3.5 or lower

Concentration: 15%. The optimal range is 10-20%; greater than 20% did not increase levels in skin.

When 15% is applied to skin, it saturates skin in 3 days, and decreases by 50% in 4 days. Once inside the skin, it cannot be removed by washing.

When combined with 1% vitamin E and 0.5% ferulic acid the stability and antioxidant effects increase by 8 fold.

Skinceuticals CE Ferulic serum has by far the most published studies of all vitamin C serums. Skinceuticals hold a patent (US Patent No. 7,179,841) on this formulation, and since then many other dupes have developed on the market but do not contain the exact formulation and often lack clinical studies.

sodium and magnesium ascorbyl phosphate

Salt forms for L-ascorbic acid. Thus, effectiveness depends on skin conversion of SAP/MAP to AA.

Optimal formulation:

pH: 7

MAP has better stability in emulsion vehicle.

Studies on efficacy have been mixed. Few studies demonstrate issues with percutaneous absorption, while other in vivo and in vitro studies show benefit.

Since these are charged molecules, formulation at neutral pH to help with skin penetration is key.

Ascorbyl Glucoside (AA-2G)

Glucose (sugar) group modified on AA to protect against photodegradation. AA-2G is converted to AA by skin enzyme α-glucosidase, giving more sustained release of vitamin C on skin. Furthermore, its less irritating than AA.

Optimal formulation:

AA-2G is only 50% as potent, compared to AA, as an antioxidant. But has comparable collagen stimulating and tyrosinase inhibiting properties.

3-O-ethyl ascorbic acid (3OAA)

Ethylated vitamin derivative. It’s stable in various temperatures and most commonly used in Asian skincare for brightening benefits.

Optimal Formulation:

Similar to AA-2G it is less effective compared to AA. It seems promising as an antioxidant and tyrosinase inhibitor, but studies are limited on its effect on neocollagenesis.

ascorbyl palmitate

Lipophilic ester form of AA. Unfortunately due to its chemical structure, the stability is similar to AA and is one of the least stable vitamin C derivatives. However it has better skin penetration given its lipophilic nature

Optimal formulation:

• pH: neutral
• Variable depending on carrier system
• Gel-cream maybe the best vehicle

It has demonstrated antioxidant and anti-aging benefits. However like MAP/SAP, there’s questionable conversion to AA in skin. Furthermore, one study has shown that ascorbyl palmitate when exposed to UVB may actually potentiate lipid oxidation, leading to more oxidative damage on skin.

Tetrahexyldecyl Ascorbate

Lipid soluble and stable form of provitamin C with enzymatic conversion to AA in skin. It has better skin penetration (4x compared to MAP). Given its lipophilic nature, it’s able to penetrate into the dermis, where AA cannot. Smaller studies suggest it may potentially be more potent than AA and less irritating.

Optimal formulation:

Ascorbyl Tetraisopalmitate (ATIP)

Similar to tetrahexyldecyl ascorbate, ATIP is another lipid soluble form of vitamin C with slightly different chemical structure. In vitro studies have shown a conversion to AA at a rate of 84%. It has great stability with a longer shelf-long of 6-12 months.

Optimal Formulation,

It can be more expensive to formulate.

Lastly, when it comes to personal use, I stick to products that are backed by clinical research. To date, Skinceuticals CE Ferulic has the most studies. Other products including Vichy Peptide C, and Skinbetter Alto Defense, and Revision C+ Correcting Complex seem promising and backed by studies.

Check out my instagram post for products in each category.

References:

Pinnell, Sheldon R., et al. “Topical L-Ascorbic Acid: Percutaneous Absorption Studies.” Dermatologic Surgery, vol. 27, no. 2, 2001, p. 137–142.,

Stamford, Nicholas P J. “Stability, Transdermal Penetration, and Cutaneous Effects of Ascorbic Acid and Its Derivatives.” Journal of Cosmetic Dermatology, vol. 11, no. 4, 2012, p. 310–317.

“Ferulic Acid Stabilizes a Topical Solution Containing Vitamins C and E and Doubles Its Photoprotection for Skin.” Journal of the American Academy of Dermatology, vol. 52, no. 3, 2005.

Lin, Jing-Yi, et al. “UV Photoprotection by Combination Topical Antioxidants Vitamin C and Vitamin E.” Journal of the American Academy of Dermatology, vol. 48, no. 6, 2003, p. 866–874.

Stamford et al. “Stability, transdermal penetration, and cutaneous effects of ascorbic acid and its derivatives.” Journal of Cosmetic Dermatology. vol. 11, 2012. pp: 310–317.