8. Int J Cosmet Sci. 2008 Dec;30(6):453-8.  Stability of vitamin C derivatives in topical formulations containing lipoic acid, vitamins A and E.  Segall AI, Moyano MA.  Cátedra de Control de Calidad de Medicamentos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina. asegall@ffyb.uba.ar 

 The stability of ascorbyl palmitate, sodium ascorbyl phosphate and magnesium ascorbyl phosphate in topical formulations was investigated by direct reverse phase high performance liquid chromatography after sample dilution with a suitable buffer - organic solvent mixture. Ascorbyl palmitate, sodium ascorbyl phosphate and magnesium ascorbyl phosphate are derivatives of ascorbic acid which differ in hydrolipophilic properties. They are widely used in cosmetic and pharmaceutical preparations. According to the results, ascorbyl esters showed significant differences: sodium ascorbyl phosphate and magnesium ascorbyl phosphate are more stable derivatives of vitamin C than ascorbyl palmitate and may be easily used in cosmetic products.  PMID: 19099546  [PubMed - indexed for MEDLINE] 

7. Skin Res Technol. 2008 Aug;14(3):376-80.  In vitro antioxidant activity and in vivo efficacy of topical formulations containing vitamin C and its derivatives studied by non-invasive methods.  Campos PM, Gonçalves GM, Gaspar LR.  Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil. pmcampos@usp.br 

 BACKGROUND/PURPOSE: Vitamins C and its derivatives, mainly due to their antioxidant properties, are being used in cosmetic products to protect and to reduce the signs of ageing. However, there are no studies comparing the effects of vitamin C [ascorbic acid (AA)] and its derivatives, magnesium ascorbyl phosphate (MAP) and ascorbyl tetra-isopalmitate (ATIP), when vehiculated in topical formulations, mainly using objective measurements, which are an important tool in clinical efficacy studies. Thus, the objective of this study was to determine the in vitro antioxidant activity of AA and its derivatives, MAP and ATIP, as well as their in vivo efficacy on human skin, when vehiculated in topical formulations. METHODS: The study of antioxidant activity in vitro was performed with an aqueous and a lipid system. The in vivo methodology consisted of the application of these formulations on human volunteers' forearm skin and the analysis of the skin conditions after 4-week period daily applications in terms of transepidermal water loss (TEWL), stratum corneum moisture content and viscoelasticity using a Tewameter, Corneometer and Cutometer, respectively. RESULTS: In vitro experiments demonstrated that in an aqueous system, AA had the  best antioxidant potential, and MAP was more effective than ATIP, whereas in the  lipid system ATIP was more effective than MAP. In in vivo studies, all formulations enhanced stratum corneum moisture content after a 4-week period daily applications when compared with baseline values; however, only the formulation containing AA caused alterations in TEWL values. The formulations containing MAP caused alterations in the viscoelastic-to-elastic ratio, which suggested its action in the deeper layers of the skin. CONCLUSION: AA and its derivates presented an in vitro antioxidant activity but AA had the best antioxidant effect. In in vivo efficacy studies, only the formulation containing AA caused alterations in TEWL values and the formulation containing MAP caused alterations in the viscoelastic-to-elastic ratio. This way, vitamin C derivatives did not present the same effects of AA on human skin; however, MAP showed other significant effect-improving skin hydration, which is very important for the normal cutaneous metabolism and also to prevent skin alterations and early ageing.  PMID: 19159387  [PubMed - indexed for MEDLINE]  

6. Biol Pharm Bull. 1999 Dec;22(12):1301-5.  Protective effects of sodium-L-ascorbyl-2 phosphate on the development of UVB-induced damage in cultured mouse skin.  Nayama S, Takehana M, Kanke M, Itoh S, Ogata E, Kobayashi S.  Kyoritsu College of Pharmacy, Tokyo, Japan. 

 The protective effect of sodium-L-ascorbyl-2 phosphate (As-2P), a stable form of  ascorbic acid (AsA), against photodamage induced by a single dose of UVB exposure (290-320 nm, Max 312 nm) was investigated using cultured mouse skin. When the cultured skin was treated with various As-2P concentrations, the cutaneous AsA level increased in proportion to the As-2P concentration. After 3 h of incubation, the AsA level in the cultured skin treated with 2, 20 and 100 mM As-2P increased 1.03-, 2.17- and 6.27-fold, respectively, compared with that of the control skin. These results suggest that As-2P was transported into the cultured mouse skin where it was converted to AsA. After 3 h, the cutaneous AsA level in irradiated (20 kJ/m2) skin was depleted to a half of that in the control skin. However, the level in skin pretreated with 20 mM As-2P was maintained within normal limits, even after 24 h. Pretreatment with 20 mM As-2P significantly prevented such photodamage as sunburn cell formation, DNA fragmentation and lipid peroxidation, which were caused by a single dose of UVB irradiation. These results suggest that the protective effect of 20 mM As-2P on UVB-induced cutaneous damage is due to the maintenance of a normal As level by conversion of As-2P to As in skin tissue.  PMID: 10746160  [PubMed - indexed for MEDLINE]  

5. Photochem Photobiol. 1998 Jun;67(6):669-75.  Postadministration protective effect of magnesium-L-ascorbyl-phosphate on the development of UVB-induced cutaneous damage in mice.  Kobayashi S, Takehana M, Kanke M, Itoh S, Ogata E.  Kyoritsu College of Pharmacy, Tokyo, Japan. kobayashi-sz@kyoritsu-ph.ac.jp 

 The effects of stable vitamin C, magnesium-L-ascorbyl-2-phosphate (MAP), administered after acute and chronic exposure to UVB irradiation were investigated using hairless mice. Intraperitoneal administration of 100 mg/kg of  MAP immediately after acute exposure to 15 kJ/m2 of UVB significantly prevented increases of UVB-induced lipid peroxidation in skin and sialic acid in serum, an  inflammation marker. Administration of 50 mg/kg of MAP immediately after each exposure significantly delayed skin tumor formation and hyperplasia induced by chronic exposure to 2 kJ/m2 of UVB. Intraperitoneal administration of 200 mg/kg of MAP produced an increase in ascorbic acid (As) levels in the serum, liver and  skin within 15 min. Serum As levels quickly returned to normal, but hepatic and cutaneous levels remained elevated before returning to normal after 24 h, suggesting that MAP was converted to As in the serum and in those tissues. Ultraviolet B-induced hydroxyl radical generation in murine skin homogenates was  scavenged by As-Na addition, which was directly detected by electron spin resonance (ESR). These results suggest that postadministration of MAP delays progression of skin damage induced by UVB irradiation. It is presumed that MAP, once converted to As, exhibits such inhibitory effects by scavenging hydroxyl and lipid radicals generated as a direct or indirect result of UVB exposure.  PMID: 9648533  [PubMed - indexed for MEDLINE]  

4. J Pharm Biomed Anal. 1997 Mar;15(6):795-801.  Stability of vitamin C derivatives in solution and topical formulations.  Austria R, Semenzato A, Bettero A.  Università di Padova, Dipartimento di Scienze Farmaceutiche, Italy. 

 The stabilityy of ascorbic acid, ascorbyl palmitate and magnesium ascorbyl phosphate (VC-PMG) in both standard solutions and topical formulations was investigated by direct RP-HPLC analysis after sample dilution with a suitable aqueous-organic solvent mixture. The results showed that, whereas the two vitamin C derivatives were more stable than ascorbic acid, the ascorbyl esters showed significant differences. Esterification with palmitic acid in 6 position did not  prevent hydrolysis of the molecule, either in solution or in emulsion; only the special preparation of products with high viscoelastic properties was able to reduce the typical behaviour of this compound. Conversely, the introduction of the phosphoric group in 2 position protected the molecule from break-up of the enediol system, confirming VC-PMG as a very stable derivative of vitamin C that may be easily used in various types of cosmetic products.  PMID: 9172105  [PubMed - indexed for MEDLINE] 

3. Photochem Photobiol. 1996 Jul;64(1):224-8.  Protective effect of magnesium-L-ascorbyl-2 phosphate against skin damage induced by UVB irradiation.  Kobayashi S, Takehana M, Itoh S, Ogata E.  Kyoritsu College of Pharmacy, Tokyo, Japan. 

 The protective effect of magnesium-L-ascorbyl-2-phosphate (MAP) on cutaneous photodamage such as lipid peroxidation and inflammation induced by ultraviolet B  (UVB) exposure (290-320 nm, max. 312 nm) was investigated using hairless mice. When MAP was administered intraperitoneally to mice at a dose of 100 mg of ascorbic acid (AS) per kg body weight base immediately before irradiation (15 kj/m2), the expected increases in thiobarbituric acid reactive substance (TBARS)  formation in skin and serum sialic acid, indices of lipid peroxidation and inflammatory reaction, respectively, were significantly reduced. However, the expected decrease in the level of cutaneous AS was unchanged. Similar results were observed for animals given 100 mg of AS-Na per kg body weight before UVB irradiation. When MAP was administered intracutaneously immediately before irradiation, the expected UVB-induced increases in TBARS and sialic acid were again significantly prevented. Ascorbic acid-Na had a less protective effect than intracutaneous MAP administration. The cutaneous AS level was significantly higher in the MAP-treated mice than in the controls, and the UVB-induced decrease in tissue AS was prevented by intracutaneous MAP administration. These results suggest that MAP protects against UVB irradiation-induced lipid peroxidation and  inflammation in cutaneous tissue, regardless of the drug administration route. We found, in an in vitro experiment, that MAP was converted to AS as it crossed the  epidermis, but that AS-Na did not pass through the epidermis. Furthermore, MAP was also converted to AS in serum. These results suggest that the protective effect of MAP on UVB-induced cutaneous damage is due to conversion of MAP to AS.  PMID: 8787018  [PubMed - indexed for MEDLINE]  

2. J Am Acad Dermatol. 1996 Jan;34(1):29-33.  Inhibitory effect of magnesium L-ascorbyl-2-phosphate (VC-PMG) on melanogenesis in vitro and in vivo.  Kameyama K, Sakai C, Kondoh S, Yonemoto K, Nishiyama S, Tagawa M, Murata T, Ohnuma T, Quigley J, Dorsky A, Bucks D, Blanock K.  Department of Dermatology, Kitasato University School of Medicine, Sagamihara, Japan. 

 BACKGROUND: An inhibitory effect of ascorbic acid (AsA) on melanogenesis has been described. However, AsA is quickly oxidized and decomposed in aqueous solution and thus is not generally useful as a depigmenting agent. OBJECTIVE: Our purpose was to examine the effect on pigmentation of magnesium-L-ascorbyl-2-phosphate (VC-PMG), a stable derivative of AsA. METHODS: Percutaneous absorption of VC-PMG was examined in dermatomed human skin, and its effect on melanin production by mammalian tyrosinase and human melanoma cells in culture was also measured. A 10% VC-PMG cream was applied to the patients. RESULTS: VC-PMG suppressed melanin formation by tyrosinase and melanoma cells. In situ experiments demonstrated that VC-PMG cream was absorbed into the epidermis and that 1.6% remained 48 hours after application. The lightening effect was significant in 19 of 34 patients with chloasma or senile freckles and in 3 of 25  patients with normal skin. CONCLUSION: VC-PMG is effective in reducing skin hyperpigmentation in some patients.  PMID: 8543691  [PubMed - indexed for MEDLINE] 

1. Skin Pharmacol. 1993;6(1):65-71.  Regulation of collagen synthesis in human dermal fibroblasts by the sodium and magnesium salts of ascorbyl-2-phosphate.  Geesin JC, Gordon JS, Berg RA.  Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854. 

 Ascorbic acid has been shown to stimulate collagen synthesis in dermal fibroblasts by increasing the rate of transcription of collagen genes. Experiments involving the use of ascorbic acid require daily supplementation due  to the instability of the molecule in aqueous solutions. In order to provide a more stable alternative to ascorbic acid, two salts of ascorbyl-2-phosphate, having a greater chemical stability than ascorbic acid, were tested for their ability to stimulate collagen synthesis in monolayer fibroblast cultures. The concentration and time dependence of their activities were compared with ascorbic acid. The magnesium salt of ascorbyl-2-phosphate was found to be equivalent to ascorbic acid in stimulating collagen synthesis in these assays, while the sodium salt required at least a tenfold greater concentration to produce the same effect as ascorbic acid. Solutions of either ascorbic acid or the ascorbyl-2-phosphate analogs (at 10 mM) in phosphate-buffered saline (PBS) were relatively stable as shown by their decay rates and their ability to stimulate collagen synthesis even after nine days in solution prior to testing their effects on cultured cells. Ascorbic acid was unstable at neutral pH compared to solutions of either sodium or magnesium ascorbyl-2-phosphate. These data support the use of magnesium ascorbyl-2-phosphate in experiments where stability of ascorbic acid is a concern, e.g. in long-term cultures or in in vivo studies.  PMID: 8489778  [PubMed - indexed for MEDLINE]  

Advanced skin care research on Magnesium Ascorbyl Phosphate (MAP) shows that it is useful for: antioxidants, anti-inflammatories, promoting collagen production, skin lightening and skin brightening, and for UV protection/sun damage repair.

Magnesium Ascorbyl Phosphate research