Retinyl Ascorbate

Retinyl Ascorbate delivers both retinoic acid and ascorbic acid to the skin. It is a very potent antioxidant, and can supplement the skin's natural antioxidant defenses against damage.

Effects


Grade Level of Evidence
A Multiple double-blind, controlled clinical trials.
B 1 double-blind, controlled clinical trial.
C At least 1 controlled or comparative clinical trial.
D Uncontrolled, observational, animal or in-vitro studies only.
Grade Effect Size of Effect Comments

D

Antioxidant

Strong

Up to 40% more potent than ascorbic acid and ascorbyl palmitate, and about 70% more potent than retinol and retinoic acid.

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Scientific Research


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Table of contents:

1. Sources

Retinyl ascorbate is the ester of retinyl chloride (a vitamin A derivative) and ascorbic acid (vitamin C).[1]

2. Bioavailability

2.1 Penetration

As a co-drug, retinyl ascorbate has a lipophilicity that is between that of ascorbic acid and retinoic acid, which is more optimal for dermal uptake.[1]

Retinyl ascorbate has good affinities for both the lipid and proteinaceous domains of the stratum corneum, giving it an advantage over retinyl palmitate, which has weaker binding to keratin and higher lipid miscibility.[2]

In one study, at least 13% of a retinyl ascorbate dose applied to full-thickness human skin penetrated the skin to various levels. After 24 hours, 6% of the retinyl ascorbate in the ester form was detected in the stratum corneum, 2% in the viable epidermis, and 0.2% in the dermis. 2% and 1.4% was delivered to the viable epidermis as retinoic acid and ascorbic acid, and likewise 0.2% and 0.15% was delivered to the dermis as retinoic acid and ascorbic acid. Compared to ascorbyl palmitate and retinyl palmitate, retinyl ascorbate penetrated the skin to a lesser degree, but was better retained inside the skin. It was suggested that this difference in retention may be due to the 5 conjugated double-bonds in the retinoid hydrocarbon backbone of retinyl ascorbate as well as the ring structure at the end of the chain, which limits its rotational flexibility and hence hinders its ability to form micelles.[1]

Retinyl ascorbate was also more easily hydrolysed to retinoic acid and ascorbic acid than the palmitate esters, with hydrolysis commencing at the uppermost levels of the viable epidermis.[1] It has been proposed that this hydrolysis is sequential, with retinyl ascorbate first chemically converted to RA-2-carboxy-2-hydroxy-ethanoate due to the presence of free radicals, then enzymatically hydrolyzed by esterases and possibly other hydrolytic enzymes.[3]

However, there is one major caveat to this study: the vehicle used was found to damage the barrier function of the stratum corneum, which would certainly influence the data collected.[1] It is also not a usable formulation, so it remains to be seen whether a usable formulation can provide the same favorable penetration and retention characteristics.

Dermal absorption of retinyl ascorbate can be improved by stretching the skin. In an experiment on porcine ear skin, delivery was improved by 20-40% when the skin was stretched, probably by forcing the hair follicles to open, thereby enhancing follicular delivery. Any process that disrupts sebum is also expected to have a positive effect, as sebum can block entry through follicle shafts.[4]

2.2 Stability

Retinyl ascorbate has only limited stability in water and methanol as well as in methanol/water and ethanol/water co-solvents. In a co-solvent system comprising 50:50 methanol and PBS at a pH of 4.8 however, it is substantially more stable than either retinoic acid or ascorbic acid, and about as stable as retinyl palmitate and ascorbyl palmitate.[1]

Retinyl ascorbate is also highly unstable on exposure to light, temperature and atmospheric oxygen.[1] It also undergoes hydrolytic reduction in the presence of free radicals, which can be ameliorated by the addition of an antioxidant such as ascorbic acid.[3]

3. Effects on the skin

3.1 Antioxidant activity

Retinyl ascorbate can enrich the skin's endogenous protection system by helping to diminish oxidative damage in the skin. When incubated with the free radical 1,1-diphenyl-picrylhydrazyl (DPPH), an in vitro model for hydroperoxyl and peroxyl radicals generated by lipid oxidation, retinyl ascorbate exhibited potent scavenging activity via an active byproduct, RA-2-carboxy-2-hydroxy-ethanoate. Significantly, retinyl ascorbate reduced DPPH at a faster rate than ascorbic acid, ascorbyl palmitate, retinoic acid and retinol, indicating that its potency is 30-40% greater than those of ascorbic acid and ascorbyl palmitate, and 70% greater than those of the retinoids.[5]

4. Safety

4.1 Toxicity

Although retinyl ascorbate had protective and regenerative properties when incubated with cultured human keratinocytes at a concentration of 6 µM when these cells were exposed to hydrogen peroxide, at concentrations above 6 µM, retinyl ascorbate became toxic, reducing the number of live cells rapidly with increasing concentration.[6] This may be a result of its powerful antioxidant properties, as excessive amounts of antioxidants such as ascorbic acid are known to have adverse effects on cells.[7][8]

Scientific References