|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|
Mitigates the formation of sunburn cells in vivo and reduces inflammation and cell death of keratinocytes in vitro.
Scavenges a variety of free radicals and protects against lipid peroxidation, but does not prevent protein carbonylation in the stratum corneum.
Inhibits melanin production in vitro but does not improve dark under-eye circles.
May improve wrinkles as it promotes collagen synthesis for prolonged periods in vitro.
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Table of contents:
Ascorbyl glucosides are important vitamin C derivatives that mainly include 5-O-D-glucopyranosyl-L-ascorbic acid (AA5G), 6-O-D-glucopyranosyl-L-ascorbic acid (AA6G), 3-O-glycosyl-L-ascorbic acid (AA3G), 2-O-D-glucopyranosyl-L-ascorbic acid (AA2αG), and 6-O-acyl-2-O-D-glucopyranosyl-L-ascorbic acid (6-acyl-AA2G). Of these, AA2αG is preferred in cosmetic applications because it is simple and cheap to synthesize, has high regiospecificity, and is easily absorbed.
Animals such as guinea pigs and rats produce AA2αG in vivo when fed ascorbic acid and maltose in combination. Rice seeds and the bacterium Bacillus stearothermophilus have also been shown to synthesize AA2αG from ascorbic acid. Kimchi, a traditional Korean fermented cabbage, contains AA2αG as well.
Another form of ascorbyl glucoside, 2-O-β-D-glucopyranosyl-L-ascorbic acid (AA2βG), has been isolated from the fruit of Lycium barbarum L., also known as goji berries or wolfberries. It can also be enzymatically synthesized from ascorbic acid using cellulase, with cellobiose as a glucose donor.
AA2αG is stable in water under aerobic conditions and is remarkably resistant against enhanced oxidative degradation by heat, copper (II) ions or ascorbate oxidase. AA2βG is also stable under acidic and oxidative conditions. Overall, its stability is optimal at a temperature of 55.3°C and at a pH of 6.4.
2.1 Topical administration
AA2αG has been shown to be percutaneously absorbed into human skin. It releases ascorbic acid over a longer period of time than ascorbyl phosphate, another vitamin C derivative. This may be due to the metabolism of AA2αG to ascorbic acid being sustained over a longer period of time, perhaps because the activity of α-glucosidase, which hydrolyzes AA2αG in the human body, is lower than that of alkaline phosphatase, which hydrolyzes ascorbyl phosphate.
Pretreating the skin with lasers promotes the transdermal delivery of ascorbyl glucoside. An erbium:YAG laser partly ablated the stratum corneum layer of nude mouse skin, increasing the flux of ascorbyl glucoside by 35 to 78-fold, whereas a carbon dioxide laser increased the flux by 82 to 117-fold, possibly via both ablation of the stratum corneum and a thermal effect. Similarly, treatment of pig skin with a fractional carbon dioxide laser enhanced the skin permeation of ascorbyl glucoside, but with less skin disruption than a conventional carbon dioxide laser.
Sodium dilauramidoglutamide lysine (DLGL), a peptide-based gemini surfactant, can also enhance the penetration and accumulation of ascorbyl glucoside in the skin.
2.2 Oral administration
AA2αG given orally is hydrolyzed by maltase in the small intestine to ascorbic acid, which is then absorbed, resulting in an increase in serum ascorbic acid levels. AA2βG is also absorbed when administered orally and is hydrolyzed to ascorbic acid by β-glucosidase.
Whether ingestion of ascorbyl glucoside increases the ascorbic acid content of the skin is unknown, however.
3. Effects on the skin
3.1 Antioxidant effect
AA2αG scavenges free radicals and protects against lipid peroxidation  but does not prevent protein carbonylation, a biomarker for oxidative stress in the human stratum corneum.
AA2βG exhibited similar antioxidant activities as AA2αG in 4 antioxidant assays, but its capacity to scavenge peroxyl and nitrite radicals were lower than that of AA2αG, and it was incapable of scavenging superoxide anion radicals.
AA2αG reduces the acute inflammation and cell death of human keratinocytes caused by UV irradiation partly by scavenging reactive oxygen species and potentiating the antioxidative action of α-tocopherol (vitamin E) after its conversion to ascorbic acid. An AA2αG cream applied to the arm once a day for 20 days also mitigated the formation of sunburn cells in 5 human volunteers irradiated with twice the minimal erythema dose compared to a placebo cream, affirming the photoprotective effects of AA2αG in vivo.
3.3 Lightening effect
Ascorbyl glucoside has been shown to inhibit the synthesis of melanin in vitro in mouse melanoma cells. The inhibition was longer-lasting than either ascorbic acid or ascorbyl phosphate, indicating that ascorbyl glucoside has a more sustained effect on skin pigmentation.
A skin lightening gel containing ascorbyl glucoside and niacinamide significantly reduced facial hyperpigmented spots in a clinical trial. This effect was boosted by the use of ultrasound radiation, which enhanced the absorption of the skin lightening agents. In addition, full-face iontophoresis of ascorbyl glucoside coupled with a mandelic/malic acid skin care regimen was an effective short-term treatment for melasma and post-inflammatory hyperpigmentation, leading to a mean 73% improvement in abnormal skin pigmentation after an average of 26 months. On the other hand, a ascorbyl glucoside lotion was not successful in reducing dark circles of the lower eyelids in another study, as it did not lead to significant differences in melanin index, erythema index or dermal thickness of the eyelids compared to vehicle.
3.4 Other age-related improvements
Ascorbyl glucoside stimulates collagen production in cultured human fibroblasts over a prolonged period, due to its sustained decomposition to ascorbic acid. It has also been demonstrated to promote cell proliferation and to reduce biomarkers of cellular senescene, such as senescence associated-β-galactosidase (SA-β-gal) activity and SIRT1 expression, induced by hydrogen peroxide. Significantly, the repetitive addition of ascorbyl glucoside to a culture of human skin epidermis keratinocytes increased their maximal population doubling level by up to 150%, presumably through suppressing DNA damage caused by reactive oxygen species and hence slowing down the shortening of telomeric DNA.
4. Side Effects
Although an adequate amount of ascorbyl glucoside is not cytotoxic, excessive amounts of ascorbyl glucoside have been shown to be cytotoxic to low density cultures of fibroblasts. It has been suggested that the abnormally accumulated ascorbic acid in cells cultured at low density may amplify the generation of oxygen radicals through the reduction of Fe(III) ions and subsequent oxidative reactions, leading to cell death.
We were not able to find any studies or reports on the safety of ascorbyl glucoside as used in cosmetic products.
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