Ascorbyl Glucoside

Ascorbyl glucoside releases vitamin C into the skin in a sustained manner, leading to more prolonged effects on the skin compared to other vitamin C derivatives.

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

C

Photoprotection

Mild

Mitigates the formation of sunburn cells in vivo and reduces inflammation and cell death of keratinocytes in vitro.

D

Antioxidant

Moderate

Scavenges a variety of free radicals and protects against lipid peroxidation, but does not prevent protein carbonylation in the stratum corneum.

D

Skin lightening

Mild

Inhibits melanin production in vitro but does not improve dark under-eye circles.

D

Wrinkle treatment

Mild

May improve wrinkles as it promotes collagen synthesis for prolonged periods in vitro.

Looking to buy skin care products containing Ascorbyl Glucoside?

Buy from Amazon.com.

Scientific Research


Caution: Please read wisderm.com's medical disclaimer.

Table of contents:

1. Sources

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.[1]

Animals such as guinea pigs and rats produce AA2αG in vivo when fed ascorbic acid and maltose in combination.[2][3][4] Rice seeds and the bacterium Bacillus stearothermophilus have also been shown to synthesize AA2αG from ascorbic acid.[5][6][7] Kimchi, a traditional Korean fermented cabbage, contains AA2αG as well.[8]

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.[9] It can also be enzymatically synthesized from ascorbic acid using cellulase, with cellobiose as a glucose donor.[10]

AA2αG is stable in water under aerobic conditions and is remarkably resistant against enhanced oxidative degradation by heat, copper (II) ions or ascorbate oxidase.[5] AA2βG is also stable under acidic and oxidative conditions.[10] Overall, its stability is optimal at a temperature of 55.3°C and at a pH of 6.4.[11]

2. Bioavailability

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.[12]

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.[13] 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.[14]

Sodium dilauramidoglutamide lysine (DLGL), a peptide-based gemini surfactant, can also enhance the penetration and accumulation of ascorbyl glucoside in the skin.[15]

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.[2][16][17][18][19] AA2βG is also absorbed when administered orally and is hydrolyzed to ascorbic acid by β-glucosidase.[9]

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[20][21][22][23][24][25] and protects against lipid peroxidation [12][22][26] but does not prevent protein carbonylation, a biomarker for oxidative stress in the human stratum corneum.[27]

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.[28][29]

3.2 Photoprotection

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.[26][30] 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.[12]

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.[12]

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.[31] 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.[32] 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.[33]

Ascorbyl glucoside stimulates collagen production in cultured human fibroblasts[34][35][36] over a prolonged period, due to its sustained decomposition to ascorbic acid.[37] It has also been demonstrated to promote cell proliferation[34][38] and to reduce biomarkers of cellular senescene, such as senescence associated-β-galactosidase (SA-β-gal) activity and SIRT1 expression, induced by hydrogen peroxide.[38] 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.[39]

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.[36]

We were not able to find any studies or reports on the safety of ascorbyl glucoside as used in cosmetic products.

Scientific References


  1. Han R, et. al. Functions, applications and production of 2-O-D-glucopyranosyl-L-ascorbic acid. Appl Microbiol Biotechnol. (2012)
  2. Muto N, et. al. Evidence for the in vivo formation of ascorbic acid 2-O-alpha-glucoside in guinea pigs and rats. Biochem Pharmacol. (1991)
  3. Yamamoto I, et. al. Formation of a stable L-ascorbic acid alpha-glucoside by mammalian alpha-glucosidase-catalyzed transglucosylation. Biochim Biophys Acta. (1990)
  4. Muto N, Nakamura T, Yamamoto I. Enzymatic formation of a nonreducing L-ascorbic acid alpha-glucoside: purification and properties of alpha-glucosidases catalyzing site-specific transglucosylation from rat small intestine. J Biochem. (1990)
  5. Yamamoto I, et. al. L-ascorbic acid alpha-glucoside formed by regioselective transglucosylation with rat intestinal and rice seed alpha-glucosidases: its improved stability and structure determination. Chem Pharm Bull (Tokyo). (1990)
  6. Tanaka M, Muto N, Yamamoto I. Characterization of Bacillus stearothermophilus cyclodextrin glucanotransferase in ascorbic acid 2-O-alpha-glucoside formation. Biochim Biophys Acta. (1991)
  7. Mandai T, et. al. The crystal structure and physicochemical properties of L-ascorbic acid 2-glucoside. Carbohydr Res. (1992)
  8. Jun HK, et. al. Formation of a L-Ascorbic acid 2-0-Glucoside during kimchi fermentation. Journal of Food Science and Nutrition. (1998)
  9. Toyoda-Ono Y, et. al. 2-O-(beta-D-Glucopyranosyl)ascorbic acid, a novel ascorbic acid analogue isolated from Lycium fruit. J Agric Food Chem. (2004)
  10. Toyada-Ono Y, et. al. A novel vitamin C analog, 2-O-(beta-D-Glucopyranosyl)ascorbic acid: examination of enzymatic synthesis and biological activity. J Biosci Bioeng. (2005)
  11. Huang WY, et. al. Stability studies of ascorbic acid 2-glucoside in cosmetic lotion using surface response methodology. Bioorg Med Chem Lett. (2013)
  12. Kumano Y, et. al. In vitro and in vivo prolonged biological activities of novel vitamin C derivative, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), in cosmetic fields. J Nutr Sci Vitaminol (Tokyo). (1998)
  13. Hsiao CY, et. al. Skin pretreatment with lasers promotes the transdermal delivery of vitamin C derivatives. Lasers Med Sci. (2011)
  14. Hsiao CY, et. al. Fractional carbon dioxide laser treatment to enhance skin permeation of ascorbic acid 2-glucoside with minimal skin disruption. Dermatol Surg. (2012)
  15. Hikima T, et. al. Skin accumulation and penetration of a hydrophilic compound by a novel gemini surfactant, sodium dilauramidoglutamide lysine. Int J Pharm. (2013)
  16. Yamamoto I, et. al. Antiscorbutic activity of L-ascorbic acid 2-glucoside and its availability as a vitamin C supplement in normal rats and guinea pigs. J Pharmacobiodyn. (1990)
  17. Muto N, Terasawa K, Yamamoto I. Evaluation of ascorbic acid 2-O-alpha-glucoside as vitamin C source: mode of intestinal hydrolysis and absorption following oral administration. Int J Vitam Nutr Res. (1992)
  18. Wakamiya H, et. al. In situ intestinal absorption of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid in guinea pigs. J Nutr Sci Vitaminol (Tokyo). (1995)
  19. Nakamura S, Oku T. Bioavailability of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid as ascorbic acid in healthy humans. Nutrition. (2009)
  20. Fujinami Y, Tai A, Yamamoto I. Radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl of ascorbic acid 2-glucoside (AA-2G) and 6-acyl-AA-2G. Chem Pharm Bull (Tokyo). (2001)
  21. Takebayashi J, et. al. Characterization of the radical-scavenging reaction of 2-O-substituted ascorbic acid derivatives, AA-2G, AA-2P, and AA-2S: a kinetic and stoichiometric study. Biol Pharm Bull. (2006)
  22. Mathew D, et. al. Ascorbic acid monoglucoside as antioxidant and radioprotector. J Radiat Res. (2007)
  23. Takebayashi J, Tai A, Yamamoto I. Long-term radical scavenging activity of AA-2G and 6-acyl-AA-2G against 1,1-diphenyl-2-picrylhydrazyl. Biol Pharm Bull. (2002)
  24. Takebayashi J, Tai A, Yamamoto I. pH-dependent long-term radical scavenging activity of AA-2G and 6-Octa-AA-2G against 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation. Biol Pharm Bull. (2003)
  25. Takebayashi J, et. al. 2-O-alpha-D-glucopyranosyl-L-ascorbic acid scavenges 1,1-diphenyl-2-picrylhydrazyl radicals via a covalent adduct formation. Biosci Biotechnol Biochem. (2007)
  26. Miyai E, et. al. Ascorbic acid 2-O-alpha-glucoside-induced redox modulation in human keratinocyte cell line, SCC: mechanisms of photoprotective effect against ultraviolet light B. Biol Pharm Bull. (1997)
  27. Tsai FJ, et. al. Evaluation of the antioxidative capability of commonly used antioxidants in dermocosmetics by in vivo detection of protein carbonylation in human stratum corneum. J Photochem Photobiol B. (2012)
  28. Takebayashi J, et. al. Antioxidant properties of 2-O-beta-D-glucopyranosyl-L-ascorbic acid. Biosci Biotechnol Biochem. (2008)
  29. Zhang Z, et. al. Comparative evaluation of the antioxidant effects of the natural vitamin C analog 2-O-β-D-glucopyranosyl-L-ascorbic acid isolated from Goji berry fruit. Arch Pharm Res. (2011)
  30. Miyai E, et. al. Ascorbic acid 2-O-alpha-glucoside, a stable form of ascorbic acid, rescues human keratinocyte cell line, SCC, from cytotoxicity of ultraviolet light B. Biol Pharm Bull. (1996)
  31. Hakozaki T, et. al. Ultrasound enhanced skin-lightening effect of vitamin C and niacinamide. Skin Res Technol. (2006)
  32. Taylor MB, et. al. Successful short-term and long-term treatment of melasma and postinflammatory hyperpigmentation using vitamin C with a full-face iontophoresis mask and a mandelic/malic acid skin care regimen. J Drugs Dermatol. (2013)
  33. Ohshima H, et. al. Effects of vitamin C on dark circles of the lower eyelids: quantitative evaluation using image analysis and echogram. Skin Res Technol. (2009)
  34. Yamamoto I, et. al. Collagen synthesis in human skin fibroblasts is stimulated by a stable form of ascorbate, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid. J Nutr. (1992)
  35. Yamamoto I, Muto N. Bioavailability and biological activity of L-ascorbic acid 2-O-alpha-glucoside. J Nutr Sci Vitaminol (Tokyo). (1992)
  36. Murakami K, et. al. Comparison of ascorbic acid and ascorbic acid 2-O-alpha-glucoside on the cytotoxicity and bioavailability to low density cultures of fibroblasts. Biochem Pharmacol. (1992)
  37. Kumano Y, et. al. Enhancing effect of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid, a stable ascorbic acid derivative, on collagen synthesis. Biol Pharm Bull. (1998)
  38. Taniguchi M, et. al. Anti-oxidative and anti-aging activities of 2-O-α-glucopyranosyl-L-ascorbic acid on human dermal fibroblasts. Eur J Pharmacol. (2012)
  39. Yokoo S, et. al. Slow-down of age-dependent telomere shortening is executed in human skin keratinocytes by hormesis-like-effects of trace hydrogen peroxide or by anti-oxidative effects of pro-vitamin C in common concurrently with reduction of intracellular oxidative stress. J Cell Biochem. (2004)