Ascorbic Acid (Vitamin C)

Ascorbic acid also known as L-ascorbic acid, has the most research of any form of vitamin C when it comes to benefits for the skin. It is a potent antioxidant and skin soothing agent that can improve the appearances of signs of ageing. It can be found in citrus fruits and green leavy vegetables. It inhibits melanin formation and reduces oxidized melanin because it's able to reduce o-DOPAquinone back to DOPA, thus avoiding melanin formation. Many of products contain vitamin C have problems with stability.

It is also a powerhouse when mixed together with other antioxidants or when it used it alone in higher concentrations such as 15%, 20% or higher, amounts that can be great for even out skin tone. This means is that you can use or layer products containing both niacinamide and vitamin C knowing that they will not render each other any less effective. Each of these ingredients on its own can help to address dark spots, uneven skin tone, wrinkles, loss of firmness, and dullness. This duo will help give you an even better chance at achieving a radiant, smooth, even, younger-looking complexion.

Physical Characteristics

Low molecular weight antioxidant molecule
L-ascorbic acid pKa 4.2
For optimal epidermal penetration, the pH must be below the pKa
Soluble in water and slightly soluble in acid
Insoluble in ether alcohols or lipids
Humans are not able to synthesise vitamin C therefore rely on dietary supplementation and topical application for dermal properties due to humans missing the final enzyme required for metabolism being L-gulono-gamma-lactone oxidase

Mechanism of Action

Transport of Vitamin C Across The Cellular Membrane

Vitamin C can cross cellular membranes by passive or active transport into the cells
Passive transport into and out of cells is via electrochemical gradients involving sodium-potassium pump pathways and other enzyme mediated systems
Active transport occurs when cells are under large amounts of stress and require large amounts of vitamin C in a short period of time
Both mechanisms of transport occur when cells are under oxidative stress
Target sites for Vitamin C are found both intercellularly and intracellularly

Antioxidant:

Free radical scavenger of reactive oxygen species
One of the most powerful antioxidants in human tissues, and is the most prevalent
Partly due to its unstable nature
It performs its antioxidant role by donating electrons to the free radicals which neutralises and makes them stable in aqueous compartments of the cell

Reduction of UVR Induced Cellular Apoptosis and DNA Damage:

Due to the antioxidant protection against reactive oxygen species and positive modulation of gene expression
UVR negatively alter genetic expression in cells which can cause cellular apoptosis and an increase in reactive oxygen species
Vitamin C activates redox-sensitive transcription factors that counteract the damage to cellular DNA that UVR cause, and therefore resists UVR induced skin damage and apoptosis
Can repair damaged DNA, however the exact mechanism is yet to be determined
UVR enhance production of matrix metalloproteinases which break down collagen, however Vitamin C decreases matrix metalloproteinase production

Stimulation of Collagen Synthesis:

Vitamin C is required for the normal formation and maintenance of collagen
Deficiency of Vitamin C leads to scurvy, which is a condition exhibiting symptoms due to collagen biosynthesis being impaired
It is essential as a cofactor enhancing prolyl and lysyl hydroxylase enzymes that work to obtain maximum stability of the collagen triple helix, ensures release of procollagen as well as being important for the cross linking of collagen fibres (Zhou et al., 2021).
Induces collagen types I and III production via activation of mRNA to encourage fibroblasts to produce collagen through enhanced transcription of the required genes
Type IV and VII collagens are slightly stimulated which form part of the dermo-epidermal junction
Improves the type I/type III collagen ratio in favour of collagen type I
Subsequent withdrawal of Vitamin C will decrease mRNA for collagen types
Stimulates fibroblast proliferation and hence collagen production
Down regulates the activation of matrix metalloproteinases to prevent the degradation of collagen (Mathew-Steiner et al., 2021).

Inhibition of Melanogenesis:

The main theory surrounding its effects on pigment formation is based upon its strong antioxidant ability by acting as a reducing agent at various stages requiring oxidation during melanin formation
Ascorbic acid has also been shown to reduce the level of quinones in the skin, such as dopaquinone, which are enzymatically generated and therefore tyrosine cannot convert this substance to melanin
Vitamin C also scavenges free radicals which can stimulate melanogenesis
Minimises oxidisation of melanin which reduces the melanin from progressing from tan to black in colour
It has also been suggested that it has an indirect activity of a tyrosinase inhibitor by stimulating p-hydroxyphenylpyruvic acid oxidase that breaks down tyrosinase. This effects melanogenesis by reducing melanin formation by tyrosine (Zheng et al., 2022).

Photoprotective Effects:

Refers to the protection of dermal tissues to UVR exposure
Requires Vitamin C to be deposited in the stratum corneum
Increases the minimal erythemal dose, which reduces cutaneous blood flow in the UV exposed area
Can reduce the formation of sunburn cells
Must be present in the skin in high enough concentrations to exert this effect both before, during and after sun exposure
Can reduce the formation of the signs of aging

Photoprotective Synergism of Vitamins C and E:

The photoprotective effects of vitamins C and E are enhanced when working together synergistically
This may be beneficial after resurfacing procedures when sunscreens are unable to be used
Vitamin C protects the aqueous compartments of the skin, such as the cytoplasm of the cell
Vitamin E protects the lipophilic compartments of the skin such as the lipid bilayer
Vitamin C is not effective against lipophilic free radicals, such as those found in intercellular lipids and lipid cell membranes, and hence works synergistically with Vitamin E (lipophilic) as a powerful antioxidant system
When used alone, L-ascorbic acid and Vitamin E provide a 2 fold photoprotective affect, however when used together they provide a 4-fold protection against UVA and UVB induced erythema (Jesus et al., 2023).
Vitamin E is less resistant to UV depletion in comparison to Vitamin C, and is replenished by being reduced by L-ascorbic acid to enable to keep providing an antioxidant action within the tissues
By combining both in a formula together it helps to stabilise it
Glutathione then regenerates L-ascorbic acid
If ferulic acid is combined with both vitamins C and E it further stabilises the formulation and provides a synergistic effect to provide an 8 fold photoprotective effect in concentrations as low at 0.5%
The photoprotective effect is noted if applied prior to and following sun exposure, however results are more pronounced when applied prior to UV exposure

Improved Barrier Function and Epidermal Hydration:

Enhances the production of ceramides
Improves the lipid lamellar structures between corneocytes (Lim, 2021).
Is involved in keratinocyte differentiation
Improves general skin ultrastructure
Improves skin hydration due to a reduction in TEWL, which thickens the epidermis due to sustaining of intra and extra cellular hydration levels (Torres et al., 2022).
Enhanced hydration aids the cell renewal process
Through a series of complex chemical reactions, ascorbic acid is converted to a form of AHA, which may mimic cell renewal effects of AHA’s.

Anti-Inflammatory Effects:

Reduces the inflammatory response when swelling is caused by reactive oxygen species
Suppresses transcription factors that are responsible for the production of pro-inflammatory cytokines by TNF e.g. IL-1, IL-6 and IL-8

Clinical Indicators

Photodamage
Acne
Rosacea
UVR exposure
Pigment disorders: ephelides, freckles, lentigines
Post inflammatory hyperpigmentation
Rhytids
Dehydrated skins
General maintenance

Formulation Considerations

Penetration rates are dose dependent
The maximum concentration required for percutaneous absorption is 20%, and higher doses do not exert any increase in absorption rates
For the product to be clinically effective it may need 8% or above of vitamin C equivalent, with 10-20% being preferable
Tissue levels may become saturated after 3 days of application
The half-life of Vitamin C after tissue saturation is 4 days

Formulation Differences

L-Ascorbic acid:

Hydrophilic form that provides the best bioavailability in the skin
Ascorbic acid penetrates the skin best at a pH less than 3-3.5 as the ionic charge is depleted
In low pH formulations can lead to irritation
Ascorbic acid can be very unstable in formulations, hence oxidation can occur. This is why Vitamin C needs to be kept in a dark, dry place with the lid tightly screwed on.
Ascorbic acid can be used effectively if its pH is below its pKa which reduces its irritating qualities (penetration over aggressiveness)

Vitamin C Esters: Ascorbyl-6-palmitate, magnesium ascorbyl phosphate (MAP)

Esters are much more stable in solutions and emulsions, which are created through esterification of the hydroxyl group
Lipophilic formulations
Beneficial for exerting effects in lipid membranes and protecting the cell membrane integrity
Penetrate deeper into the skin through the epidermis and the dermis exerting antioxidant and dermal effects
Beneficial for hypersensitive clients due to slower absorption rates

Magnesium ascorbyl phosphate:

Penetrates well to the dermis due to its lipophilic nature, and converts to L-ascorbic acid at the site of action
MAP demonstrated protect against UVB lipid peroxidation
MAP has demonstrated, in vitro, to stimulate collagen synthesis at an equivalent rate to ascorbic acid
The most stable form of Vitamin C

Ascorbyl-6-palmitate

Activity is not dependent upon breaking down to L-ascorbic acid
Topical ascorbyl-6-palmitate prove to be 30 times more effective than ascorbic acid as a tumour inhibitor in mice
Ascorbyl-6-palmitate is moderately stable

Sodium L-ascorbyl-2-phosphate (APS)

Stable hydrophilic ester derivative of L-ascorbic acid
Enzymatically converted to L-ascorbic acid in the skin
Increases intracellular cytoplasm levels of L-ascorbic acid

REFERENCES

Jesus, A., Mota, S., Torres, A., Cruz, M. T., Sousa, E., Almeida, I. F., & Cidade, H. (2023). Antioxidants in Sunscreens: Which and What For?. Antioxidants (Basel, Switzerland), 12(1), 138. doi:https://doi.org/10.3390/antiox12010138

Lim, K. M. (2021). Skin Epidermis and Barrier Function. International journal of molecular sciences, 22(6), 3035. doi:https://doi.org/10.3390/ijms22063035

Markiewicz, E., Karaman-Jurukovska, N., Mammone, T., & Idowu, O. C. (2022). Post-Inflammatory Hyperpigmentation in Dark Skin: Molecular Mechanism and Skincare Implications. Clinical, cosmetic and investigational dermatology, 15, 2555-2565. doi:https://doi.org/10.2147/CCID.S385162

Mathew-Steiner, S. S., Roy, S., & Sen, C. K. (2021). Collagen in Wound Healing. Bioengineering (Basel, Switzerland), 8(5), 63. doi:https://doi.org/10.3390/bioengineering8050063

Nowicka, D., Chilicka, D., Dzieńdziora-Urbińska, I., & Szygula, R. (2022). Skincare in Rosacea from the Cosmetologist's Perspective: A Narrative Review. Journal of clinical medicine, 12(1), 115. doi:https://doi.org/10.3390/jcm12010115

Pandey, A., Jatana, G. K., & Sonthalia, S. (2023). Cosmeceuticals. StatPearls Publishing [Internet]. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK544223/

Torres, A., Rego, L., Martins, M. S., Ferreira, M. S., Cruz, M. T., Sousa, E., & Almeida, I. F. (2023). How to Promote Skin Repair? In-Depth Look at Pharmaceutical and Cosmetic Strategies. Pharmaceuticals (Basel, Switzerland), 16(4), 573. doi:https://doi.org/10.3390/ph16040573

Twarda-Clapa, A., Olczak, A., Bialkowska, A. M., & Koziolkiewicz, M. (2022). Advanced-Glycation End-Products (AGEs): Formation, Chemistry, Classification, Receptors, and Diseases Related to AGEs. Cells, 11(8), 1312. doi:https://doi.org/10.3390/cells11081312

Videira, I. F., Moura, D. F., & Magina, S. (2019). Mechanisms regulating melanogenesis. Anais brasileiros de dermatologica, 88(1), 76-83. doi:https://doi.org/10.1590/s0365-05962013000100009

Zheng, W., Li, H., Go, Y., Chan, X. F., Huang, Q., & Wu, J. (2022). Research Advances on the Damage Mechanism of Skin Glycation and Related Inhibitors. Nutrients, 14(21), 4588. doi:https://doi.org/10.3390/nu14214588

Zhou, S., Wang, Q., Huang, A., Fan, H., Yan, S., & Zhang, Q. (2021). Advances in Skin Wound and Scar Repair by Polymer Scaffolds. Molecules (Basel, Switzerland), 26(20), 6110. doi:https://doi.org/10.3390/molecules26206110