Magnesium Ascorbyl Phosphate

Magnesium ascorbyl phosphate is a more stable derivative of Vitamin C. It has well-documented effects on skin lightening, hydration and like Vitamin C, appears to protect the skin from UV radiation.

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

Melasma treatment

Moderate

Decreases melasma severity and area, partly through suppressing melanin production by the tyrosinase enzymes.

D

Increased skin hydration

Moderate

Enhanced the moisture content of the strateum corneum, possibly through thickening of the epithelium and stimulating collagen synthesis.

D

Photoprotection

Moderate

Protects keratinocytes against UVA irradiation, possibly via increasing the levels of glutathione.

D

Skin lightening

Mild

Whitens both normal skin and senile freckles in some individuals.

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Scientific Research


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Table of contents:

1. Sources

Magnesium ascorbyl phosphate (MAP) is a derivative of vitamin C, ascorbic acid. It is produced by chemical modification of ascorbic acid; specifically, by introducing a phosphate group into the enediol system at the 2-position.[1]

When used as an active ingredient in cosmetic formulations, its concentration is usually around 1-2%, and when used as an antioxidant to stabilize formulations, its concentration ranges from 0.05-0.1% in general.[2]

2. Bioavailability

Because ascorbic acid is an unstable molecule that can be impractical to formulate for topical use, its derivatives such as MAP have been utilized in many topical formulations.[3] Chemically, MAP is more stable than ascorbic acid -- the phosphate group in the 2-position seems to protect the enediol system of MAP from hydrolysis. 1% MAP solution experienced only small concentration losses of 5% and 17% after 60 days of storage at room temperature and at 42°C, as compared to 1% ascorbic acid and 1% ascorbyl palmitate, which lost 63% and 100%, and 23% and 53% respectively, under the same conditions.[1] In another study, the shelf life of an MAP-containing emulsion formulation has been estimated to be 200 days.[4]

In one study on human skin, MAP is absorbed from a cream base into the epidermis and dermis, but the percutaneous penetration is low, with only 1.6% detected 48 hours after application. This is improved by the addition of 1% or 3% 1,1-methyleneglycol-bis to the formulation.[5] Laser pretreatment of the skin reduces the thickness of the strateum corneum, and has been shown to enhance the skin permeation and hence topical delivery of vitamin C and its derivatives, including MAP. The transdermal flux of MAP across intact skin is comparable with that of ascorbic acid,[6] but increases by 48-123-fold if the skin is pretreated with a erbium:yttrium-aluminum-garnet (Er:YAG) laser, and 116-156-fold if the skin is pretreated with a carbon dioxide laser.[6][7]

Lauroyl/palmitoyl glycol chitosan (GCL/GCP) gels also enhance the sustained release and the skin penetration and deposition of MAP in comparison with other vehicles such as glycol chitosan, hydroxypropylmethylcellulose, and carbopol. Moreover, the epidermal to dermal drug deposition ratio tends to increase with the increase in polymer concentration, which is beneficial to the activity of MAP in the epidermis, including the inhibition of tyrosinase and protection from UV damage.[8]

MAP is converted to L-ascorbic acid, the biologically active form of vitamin C, by phosphatase enzymes in the skin as it crosses the epidermis.[9][10]

It is important to note that the formulation appears to play an important role in the skin bioavailability of MAP, as a commercial serum containing 13% MAP (Vivifying Serum C) did not increase skin levels of ascorbic acid when applied to pigs.[3]

3. Effects on the skin

3.1 Lightening effect

MAP suppresses melanogenesis by tyrosinase in a dose-dependent manner in vitro. When human melanoma cells were cultured with 1% MAP for 3 days, melanin formation was reduced by 48%. In vivo, a cream containing 10% MAP had significant lightening effects on senile freckles, as well as in 3 out of 25 patients with normal skin.[5]

A whitening product containing 3% MAP + vitamin A (Concentré Anti-taches Nuit) has been tested on Japanese women. In one trial of 12 women, delayed tanning was induced in 3 sites on the left upper inner arm by exposure to solar-simulated radiation, 3 times a day for 6 weeks. Each time, the product was applied on one site 6-8 hours post-irradiation, the vehicle to another and the last site was left untreated. After 6 weeks, the areas where the product had been applied were significantly paler than the untreated areas, but the product-applied sites did not differ significantly from the vehicle-applied sites.[11] In another trial of 15 women, Concentré Anti-taches Nuit lightened the forehead and left cheek of 8 women (53%) after 6 weeks of application.[12]

3.2 Melasma treatment

Melasma is an acquired hyperpigmentation disorder for which treatment with conventional therapies are often unsatisfactory.[13]

The combination of topical 5% MAP with fluorescent pulsed light (FPL) also appears to to be effective and safe in treating refractory melasma in Asian patients, though maintenance treatments are required for persistent improvement. Patients treated for 12 weeks with 5% topical MAP and 3 sessions of FPL experienced a decrease in melasma area and severity. The study employed only subjective assessments, however.[13]

Another study showed that 10% MAP cream induced a significant lightening effect in 19 out of 34 patients with melasma. In situ experiments in the same study demonstrated that 10% MAP cream inhibits melanin production in human skin through suppression of melanin formation by tyrosinase, leading to the lightening effect.[5]

3.3 Increased moisture

Experiments indicate that MAP can improve skin hydration. Like ascorbic acid, cosmetic formulations containing MAP have been shown to enhance the moisture content of the strateum corneum after 4 weeks of daily application on the forearms of human volunteers. The formulations with MAP also caused alterations in the viscoelastic-to-elastic ratio, suggesting that its actions occur in the deeper layers of the skin.[14] A follow-up study evaluating cosmetic formulations containing a dispersion of liposomes with MAP, alpha lipoic acid and kinetin found the same effects of increased strateum corneum skin moisture and pronounced hydration effects in deeper skin layers.[15] MAP has also been demonstrated to cause a thickening of the epithelium when tested on pig skin, and to stimulate collagen synthesis in human dermal fibroblasts,[16][17] suggesting 2 possible mechanisms by which MAP results in improved hydration.[18]

3.4 Photoprotection

In vitro studies suggest that MAP, like ascorbic acid, can protect the skin against UV radiation and UV radiation-induced photodamage on the skin. In a study on hairless mice, MAP administered intracutaneously or intraperitoneally before irradiation led to significant reductions in the expected increases of thiobarbituric acid reactive substance (TBARS) formation in skin and serum sialic acid, indices of lipid peroxidation and inflammatory reaction, respectively. Ascorbic acid levels were also significantly higher in MAP-treated mice than in the controls, indicating that the protective effect is due to the conversion of MAP to ascorbic acid.[9] Intraperitoneal administration of MAP immediately after UVB exposure also prevented increases in lipid peroxidation in the skin and delayed skin tumour formation and hyperplasia.[19] Another study found that MAP and coenzyme Q10 can protect keratinocytes against UVA irradiation, possibly by increasing the levels of glutathione.[20]

4. Side Effects

The Cosmetic Ingredient Review Expert Panel considers MAP to be structurally and functionally similar to ascorbic acid, and that the data on ascorbic acid's lack of irritancy and sensitization can be extrapolated to MAP.[21] However, in our view there have not been sufficient clinical trials done on human subjects to definitively conclude on the tolerability and possible side effects attributable to topical application of MAP.

Scientific References


  1. Austria R, Semenzato A, Bettero A. Stability of vitamin C derivatives in solution and topical formulations. J Pharm Biomed Anal. (1997)
  2. Smaoui S, Ben Hlima H, Kadri A. Application of l-Ascorbic Acid and its Derivatives (Sodium Ascorbyl Phosphate and Magnesium Ascorbyl Phosphate) in Topical Cosmetic Formulations: Stability Studies. J Chem Soc Pak. (2013)
  3. Pinnell SR, et. al. Topical L-ascorbic acid: percutaneous absorption studies. Dermatol Surg. (2001)
  4. Goncalves GMS, Maia Campos PMBG. Shelf life and rheology of emulsions containing vitamin C and its derivatives. Rev Ciênc Farm Básica Apl. (2009)
  5. Kameyama K, et. al. Inhibitory effect of magnesium L-ascorbyl-2-phosphate (VC-PMG) on melanogenesis in vitro and in vivo. J Am Acad Dermatol. (1996)
  6. Lee WR, et. al. Lasers and microdermabrasion enhance and control topical delivery of vitamin C. J Invest Dermatol. (2003)
  7. Huang CH, et. al. Transdermal delivery of three vitamin C derivatives by Er:YAG and carbon dioxide laser pretreatment. Lasers Med Sci. (2013)
  8. Wang PC, et. al. Lauroyl/palmitoyl glycol chitosan gels enhance skin delivery of magnesium ascorbyl phosphate. J Cosmet Sci. (2013)
  9. Kobayashi S, et. al. Protective effect of magnesium-L-ascorbyl-2 phosphate against skin damage induced by UVB irradiation. Photochem Photobiol. (1996)
  10. Maria Campos PMBG, Silva GM. Ascorbic acid and its derivatives in cosmetic formulations. Cosmet Toil. (2000)
  11. Kawada A, et. al. An Evaluation of Whitening Effect of Concentre Anti-Tache Nuit against Solar Simulated Radiation-Induced Delayed Tanning. Skin Research. (2001)
  12. Kawada A, et. al. A new approach to the evaluation of whitening effect of a cosmetic using computer analysis of video-captured image. J Dermatol Sci. (2002)
  13. Shaikh ZI, Mashood AA. Treatment of refractory melasma with combination of topical 5% magnesium ascorbyl phosphate and fluorescent pulsed light in Asian patients. Int J Dermatol. (2014)
  14. Campos PM, Gonçalves GM, Gaspar LR. In vitro antioxidant activity and in vivo efficacy of topical formulations containing vitamin C and its derivatives studied by non-invasive methods. Skin Res Technol. (2008)
  15. Campos PM, et. al. Efficacy of cosmetic formulations containing dispersion of liposome with magnesium ascorbyl phosphate, alpha-lipoic acid and kinetin. Photochem Photobiol. (2012)
  16. Geesin JC, Gordon JS, Berg RA. Regulation of collagen synthesis in human dermal fibroblasts by the sodium and magnesium salts of ascorbyl-2-phosphate. Skin Pharmacol. (1993)
  17. Hata R, Senoo H. L-ascorbic acid 2-phosphate stimulates collagen accumulation, cell proliferation, and formation of a three-dimensional tissuelike substance by skin fibroblasts. J Cell Physiol. (1989)
  18. Silva GM, Maia Campos PM. Histopathological, morphometric and stereological studies of ascorbic acid and magnesium ascorbyl phosphate in a skin care formulation. Int J Cosmet Sci. (2000)
  19. Kobayashi S, et. al. Postadministration protective effect of magnesium-L-ascorbyl-phosphate on the development of UVB-induced cutaneous damage in mice. Photochem Photobiol. (1998)
  20. Hwang TL, et. al. Magnesium ascorbyl phosphate and coenzyme Q10 protect keratinocytes against UVA irradiation by suppressing glutathione depletion. Mol Med Rep. (2012)
  21. Elmore AR. Final report of the safety assessment of L-Ascorbic Acid, Calcium Ascorbate, Magnesium Ascorbate, Magnesium Ascorbyl Phosphate, Sodium Ascorbate, and Sodium Ascorbyl Phosphate as used in cosmetics. Int J Toxicol. (2005)