Healthy skin is characterized by a high concentration of vitamin C, much higher than that in plasma, which suggests active accumulation from the circulation. There is more in the epidermis than in the dermis (2-5 times the difference between these layers).
Vitamin C levels are lower in aging or photo-damaged skin. However, whether this relationship reflects cause or effect has not been established.
The factors that lower the level of vitamin C in the skin are, above all, excessive exposure to oxidative stress caused by pollution and UV radiation.
Bioavailability and absorption of vitamin C through the skin
Uptake of vitamin C from plasma and transport to the skin layers is mediated by specific sodium-ascorbate co-transporters (SVCT), which are present throughout the body and responsible for transportation to other tissues.
Transporters are hydrophobic membrane proteins that co-transport sodium, driving vitamin C uptake into cells.
Lower stores of vitamin C are found in tissues when plasma levels are below saturation. After plasma saturation is reached, vitamin C levels do not rise further. Dietary supplementation will effectively increase the level of vitamin C in the skin only in people whose plasma concentration is below saturation before the intervention.
Vitamin C deficiency
Vitamin C deficiency is associated with the loss of many vital functions of the skin:
- poor wound healing,
- thickening of the stratum corneum,
- subcutaneous bleeding (due to loss of connective tissue morphology).
In addition, the skin is dry, rough, and corneous.
Potential functions of vitamin C in the skin
1. Promotion of collagen formation
Vit. C acts as a cofactor for proline and lysine hydroxylases, which stabilize the collagen molecule’s tertiary structure and promote the expression of collagen genes. In the skin, collagen formation is mainly carried out by fibroblasts in the dermis. In the case of vitamin C deficiency, both the synthesis and cross-linking collagen are reduced. Moreover, vit. C stimulates the mRNA collagen production by fibroblasts.
Skin fibroblasts are entirely dependent on vit. C in the case of collagen synthesis.
Supplementation with vit. C shows an improvement in collagen synthesis in vivo.
2. Neutralization of free radicals and removal of toxic oxidants
Vit.C is a powerful antioxidant that can neutralize and scavenge free radicals from environmental pollutants and ultraviolet radiation exposure. Vit. C is especially effective in reducing oxidative damage to the skin when combined with vitamin E (Vit. C is a regenerator of oxidized vitamin E). Vit. C effectively regenerates this important lipid-soluble radical scavenger and limits oxidative damage to cell membrane structures.
3. Inhibition of melanogenesis
Vitamin C derivatives, including magnesium phosphate ascorbyl, inhibit melanin (skin pigment) synthesis by inhibiting tyrosinase, an enzyme that catalyzes the formation of skin pigment. Vitamin C can reduce ortho-quinone (intensely colored chemicals) produced by tyrosinase, but other mechanisms are also possible.
4. Interaction with cell signaling pathways
Witamin C:
- play a role in the differentiation of keratinocytes,
- improves the structural organization of the stratum corneum, which is accompanied by an increased barrier function (increases the number of keratohyalin granules – grains made of keratin proteins and the level of filaggrin – a precursor of the natural moisturizing factor NMF),
- supports the synthesis and organization of barrier lipids,
- stimulates the proliferation and migration of skin fibroblasts, which are essential for effective wound healing,
- stimulates the synthesis of glycosaminoglycans as part of the formation of the ECM extracellular matrix.
5. Modulation of epigenetic pathways
Vit. C acts as a cofactor for the Ten-Eleven Proteins (TET) family of translocation enzymes that catalyze the removal of methylated cytosine by hydroxylating it to 5-hydroxymethylcytosine (5 hmC).
- treatment with vitamin C increases the content of 5 hmC in melanoma cell lines, causing a transcriptome change and a reduction in the malignant phenotype,
- vit. C protects against UV-induced apoptosis of epidermal cells.
6. Prevention of skin aging
Protection against damage caused by exposure to UV radiation is mainly related to the antioxidant effect of vitamin C (both topically and orally). Vit. C prevents lipid peroxidation in skin keratinocytes, protects cells against apoptosis, and increases survival.
There is a synergy between vitamin C and vitamin E. Keratinocytes can store high concentrations of vitamin C, which, combined with vitamin E, protects against UV radiation. The effectiveness of topical vitamin C may depend on your initial condition. When the state of health is optimal, vit. C after topical application is not absorbed.
Studies have shown that the intake of 100 mg of vitamin C / day causes a significant increase in anti-radical activity by 22%. In turn, 180 mg/day consumption even causes a substantial boost of 37%.
Vit. C plays a role in forming the stratum corneum, thus indirectly protecting the skin against water loss (reduces TEWL – transepidermal water loss). It induces the differentiation of keratinocytes, protects cells against apoptosis, and increases their survival.
Vit. C prevents lipid peroxidation and stimulates the production of barrier lipids in skin keratinocytes.
6.1 Wrinkles
Protection against wrinkle formation mainly consists in stimulating collagen synthesis, especially in tobacco smokers. Smokers have low plasma vitamin C levels.
It has been shown that 6-palmitoyl-L-ascorbic acid (ascorbyl palmitate) reduces the visibility of wrinkles, cracks, fissures, and swelling around the eyes, and 6-O-stearoyl-L-ascorbic acid delays skin aging and is a strong inhibitor of hyaluronidase enzymes.
Some studies indicate that topical application of vitamin C can reduce skin roughness.
7. Wound healing
The significant impact of vit. C for wound healing is associated with the activity of this vitamin as a cofactor in collagen synthesis and wound healing disorders are an early indicator of hypovitaminosis C. Supplementation with vitamin C, and vitamin E improves the rate of burn wound healing. The topical application of vitamin C in silicone gel has been shown to significantly reduce the formation of permanent scarring in the Asian population.
8. Skin inflammation
The anti-inflammatory properties in supplements and cosmetics have not been documented.
Increased vitamin C utilization is observed in many inflammatory conditions, and decreased levels of this vitamin negatively affect many essential body reactions. There is a significant deterioration in vitamin C status in people with atopic dermatitis (AD), with low levels of vitamin C in the plasma. There is also a relationship between vitamin C level in plasma and the ceramide content in the epidermis of people suffering from AD. Ceramide is the major lipid in the stratum corneum. Vit. C stimulates the production of ceramides in keratinocytes by modulating the enzymes CERS related to the metabolism of ceramides, which may improve the overall function of the epidermal barrier.
Numerous studies documented that skin health positively correlates with fruit and vegetable consumption. The active ingredient in fruit and vegetables responsible for benefits has not yet been identified, although vitamin C levels are closely related to the consumption of fruit and vegetables.
The human skin condition can be improved by providing vitamin C in both oral supplements and topical applications.
SUPPLEMENTATION
Supplementation with vitamin C reduces oxidative stress parameters by neutralizing reactive oxygen species by modulating redox reactions in animal models. In addition, it accelerates bone healing after fracture and increases the synthesis of type I collagen.
No animal or human studies have shown any negative effects of vitamin C supplementation. Oral supplementation with this vitamin appears to be safe
TOPICAL APPLICATION
When plasma levels are low, some of the vit. C can be delivered to the epidermis by topical application, although its effectiveness depends on cosmetics’ composition and absorption enhancer. Vit. C, as a water-soluble and charged molecule, is repelled by the physical epidermis barrier. Only when the pH is below 4 and the vitamin C is in the ascorbic acid form does some penetration occur.
Encapsulation of vitamin C in the form of a liposphere may aid transport to the lower epidermis and increase uptake. However, the most crucial issue for the efficacy of topical application is the condition of the patient’s plasma: if plasma levels are saturated, topical application of this vitamin does not increase its content in the skin.
INTERESTING FACTS
The most significant increase in the epidermis thickness is caused by applying preparations containing the complex of vitamin C and squalene (Vit. C-SQ). Squalene is a component of sebum and the epidermal lipid barrier.
The studies show that the content of collagen III protein was twice as high in the papillary layer of the dermis after 10 days of treatment with Vit.C-SQ compared to the untreated control.
This complex regulates the components of the extracellular matrix ECM. It stimulates 6 times more expression of the metalloproteinase inhibitor TIMP and twice more expression of COL3A (a gene involved in the production of type III collagen) than the expression of the MMP1 transcript, which encodes collagenase involved in the degradation of type I and III collagen. Such effects may contribute to the preservation of existing collagen. In addition, Vit C-SQ influences the expression of decorin on the surface of collagen fibers, thus protecting them against fission by metalloproteinases.
Vit C-SQ stimulates the biosynthesis of hyaluronic acid HA in the pathway of overexpression of hyaluronan synthase HAS2 (the main skin synthase participating in the hyaluronic acid synthesis). HA strongly binds water in the skin and therefore improves skin hydration. Vit C-SQ also triggers the expression of the gene encoding adiponectin (ADIPOQ), which promotes HA biosynthesis. The epidermis thickens as adiponectin stimulates cell growth and tissue remodeling by binding and sequestering growth factors.
The complex of Vit C and squalene has a more beneficial effect on human skin compared to free Vit C or Vit C associated with palmitic acid. Vit. C, by binding to SQ, may also promote skin penetration and possible interactions with cell membranes.
