|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|
More effective than vitamin E or calcium ascorbate. May inhibit the degradation of hyaluronic acid, which has an enormous capacity to bind water in the skin.
Helps regenerate vitamin E in the skin. Also scavenges other free radicals and inhibits membrane lipid peroxidation.
Increased collagen synthesis more quickly and to a greater extent than ascorbic acid in in vitro studies on human skin and muscle cells.
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Table of contents:
Because ascorbic acid (vitamin C) is inherently unstable, it is commonly chemically modified by esterification of the hydroxyl group with long-chain acids to produce more stable molecules. One such ester is ascorbyl palmitate, which is usually formed from ascorbic acid and palmitic acid in a chemical- or enzyme-catalyzed reaction.
Still, ascorbyl palmitate is less stable than other derivatives of ascorbic acid including magnesium ascorbyl phosphate and sodium ascorbyl phospate, as esterification at the 6 position does not prevent hydrolysis of the molecule. In an accelerated aging test, 1% ascorbyl palmitate solution had a significant concentration loss after 60 days of storage (77% recovery when stored at room temperature and 47% recovery when stored at 42°C). This was better than ascorbic acid (37% recovery when stored at room temperature and none when stored at 42°C) but worse than magnesium ascorbyl phosphate (95% recovery when stored at room temperature and 83% recovery when stored at 42°C). Ascorbyl palmitate is also less stable than magnesium ascorbyl phosphate in cosmetic products. Magnesium ascorbyl phosphate in a cosmetic emulsion kept its stability by up to 95% even after 60 days of storage in the dark at 42°C, but ascorbyl palmitate showed great instability (27% recovery) under the same conditions.
Several methods can be employed to improve the stability of ascorbyl palmitate. The structural properties of the formulation matters; a cream-gel vehicle seems to be a more suitable vehicle than oil-in-water emulsions. Incorporating ascorbyl palmitate into colloidal carrier systems such as microemulsions, liposomes and solid lipid nanoparticles also helps, especially in systems where the hydrophilic part of ascorbyl palmitate is exposed to a less polar environment. In an analysis of chemical stability, ascorbyl palmitate was found to be most resistant to oxidation in non-hydrogenated soybean lecithin liposomes, followed by solid lipid nanoparticles, microemulsions, and hydrogenated soybean lecithin liposomes. Adding the co-antioxidant 4-(tridecyloxy)benzaldehyde oxime (TDBO) to oil-in-water microemulsions of ascorbyl palmitate increases its stability as well.
Storage temperature is also important; ascorbyl palmitate kept at 4°C is more stable than at room temperature or at 40°C. Exposure to light also accelerates the degradation of ascorbyl palmitate, whereas a high concentration of ascorbyl palmitate reduces the extent of its degradation.
Ascorbyl palmitate has lipophilic properties due to its hydrophobic palmitate side chain that may allow it to penetrate the stratum corneum. When applied topically to the skin of guinea pigs, ascorbyl palmitate penetrated the skin barrier, increasing the ascorbic acid content of the skin, liver and blood by 8-fold, 7-fold and 4-fold respectively. It has also been shown to penetrate to the epidermis and dermis of human skin, and has even been used as a skin permeation enhancer.
The combined use of a negative lipogel with electrical assistance can enhance the skin delivery of ascorbyl palmitate. Ascorbyl palmitate can also be encapsulated into lamellar liquid crystalline systems, nanoparticles, nanostructured lipid carriers, nanosuspensions and nanoemulsions for dermal delivery. Nanocarriers fabricated from a curcumin-grated polyvinyl polymer have been shown to be trapped in the shunts of hair follicles and to delay the degradation of ascorbyl palmitate, indicating that they can create a reservoir, slowly supplying the skin with undegraded ascorbyl palmitate.
It is important to note that the formulation appears to play an important role in the bioavailability of ascorbyl palmitate, as a commercial product containing 10% ascorbyl palmitate (Jan Marini C-Esta Serum) failed to increase skin levels of ascorbic acid in an experiment on white Yorkshire pigs.
3. Effects on the skin
3.1 Antioxidant effect
Ascorbyl palmitate can function as an antioxidant in cosmetic formulations, particularly those containing vegetable oils with high concentrations of unsaturated fatty acids. It was a more potent antioxidant than ascorbic acid in an artificial membrane, but has been found to be less potent than ascorbic acid on the human stratum corneum.
Ascorbyl palmitate regenerates α-tocopherol (a form of vitamin E), a classical lipophilic antioxidant, by reducing α-tocopheroxyl radicals more effectively than many natural phenolic compounds such as epicatechin and gallic acid, and as effectively as epigallocatechin gallate (EGCG), the major polyphenol found in green tea extract. It is also capable of scavenging hydroxyl radicals and the semiquinone radicals generated by hydroquinone. In a a common antioxidant assay, its radical scavenging activity was found to be slightly lower than those of ascorbic acid and α-tocopherol.
Ascorbyl palmitate also prevents membrane lipid peroxidation and can protect cells from the cytotoxic effects of linoleic acid hydroperoxide, one of the main products of lipid peroxidation. These properties enable ascorbyl palmitate to block the oxidation of tocopherol in erythrocytes and platelets. 
3.2 Increased hydration
Ascorbyl palmitate has considerable moisturizing activity in conventional topical formulations; a 5% ascorbyl palmitate cream was more effective than 5% calcium ascorbate and as effective as a commercial topical preparation containing vitamin E. It also works well when incorporated in solid lipid nanoparticles, nanostructured lipid carriers or nanoemulsions, due to the occlusive effect of these carriers that improves its skin moisturizing potential.
Moreover, ascorbyl palmitate is a strong inhibitor of hyaluronidases, enzymes that degrade hyaluronic acid. This is significant as hyaluronic acid is an important component of the extracellular matrix and is the key molecule involved in skin moisture due to its unique capacity to bind and retain water molecules.
Unlike ascorbic acid, ascorbyl palmitate is not a particularly good photoprotectant. Although it decreased the UV-induced formation of free radicals and inhibited lipid peroxidation in experiments on pig skin, it was not as effective as ascorbic acid in protecting against UV-induced chronic skin damage in hairless mice and only poorly inihibited UV-induced skin erythema in humans compared to vitamin E and vitamin E acetate. One study even found that ascorbyl palmitate strongly promoted UV-induced lipid peroxidation and cytotoxicity in keratinocytes, indicating that it may intensify skin damage following physiologic doses of UV radiation despite its antioxidant properties.
3.4 Collagen synthesis
Ascorbyl palmitate may be able to ameliorate wrinkles, as it has been demonstrated to markedly stimulate collagen synthesis. In human intestinal smooth muscle cells, both ascorbic acid and ascorbyl palmitate raised collagen synthesis by 2.7-fold at a concentration of 20 µM, but ascorbyl palmitate increased collagen synthesis by 2-fold at 2.5 and 5 µM concentrations, whereas 4-5 times the concentration of ascorbic acid was required to induce the same response. Similarly, human fibroblasts treated with 10 µM ascorbyl palmitate for 36 hours exhibited collagen production that was 3-fold greater than that in the presence of 10 µM ascorbic acid, though by 48 hours there were no significant differences.
4. Side Effects
Ascorbyl palmitate is generally considered a safe cosmetic ingredient. In guinea pigs, the median lethal dose was > 3 g/kg. An aqueous 10% ascorbyl palmitate solution did not cause irritation or sensitization to the skin or the eyes of rabbits in clinical studies. Similarly, an eye cream containing 0.2% ascorbyl palmitate did not cause dermal sensitization in a human maximization test. Ascorbyl palmitate was also not sensitizing to humans at concentrations of 1-5%.
Although one study indicated that ascorbyl palmitate may be potentially carcinogenic, many other studies have shown that it is not mutagenic, inhibits tumour promotion on mouse skin and exerts cytotoxic effects on cancer cells.
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