Why vitamin C should be a staple in your skincare routine

Vitamin C is one of the best researched skincare ingredients and is well-known for its significant benefits for the skin. It is the most abundant (primary) anti-oxidant in human skin [1] and necessary for collagen production. However, we are not able to synthesize vitamin C ourselves, as humans lack the enzyme L-gulonolactone oxidase necessary for synthesizing Vitamin C [2]. Thus we rely on food, supplementation or topical application [3]. 10% vitamin C in your serum is 200 x more concentrated than 1 orange. There are many compelling reasons to incorporate vitamin C in your skincare regimen, whether you are twenty or eighty. 
 
VITAMIN C (ASCORBIC ACID)
Vitamin C, also known as ascorbic acid, plays a crucial role in collagen synthesis and maintenance, significantly influencing skin health and structural integrity. Vitamin C´s efficacy is dose-dependant, more efficacy in higher concentrations, which range between 3-20%. If you´re considering a collagen stimulating (or biostimulating) aesthetic treatment, it is highly recommended to have vitamin C either in your diet or skincare regimen (day, night or both). This is beneficial for younger, however especially more mature rejuvenators as vitamin C levels are lower in mature or photo-damaged skin [4].  More vitamin C is found in epidermis which is the top layer of the skin compared to the deeper layer or dermis [5]. Oxidative stress (from pollutants or UV irradiation) is associated with depleted vitamin C levels in the epidermal layer [6].  Topical ascorbic acid is favored in the practice of dermatology [1]. Vitamin C has multiple benefits, it enhances production of barrier lipids – decreasing TEWL (transepidermal water-loss) [7] , supports differentiation of keratinocytes (skin regeneration) [8] and protects keratinocytes from apoptosis (cell death), thus increases cell survival [9], supports wound healing, and increases dermal papillae. Dermal papillae provide nutrients and oxygen to the epidermis through their rich vascular network, support epidermal-dermal adhesion, and play a crucial role in regulating hair follicle development and cycling.

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THE ROLE OF VITAMIN C IN COLLAGEN PRODUCTION
1. Transcriptional activation: Vitamin C directly activates transcription factors involved in collagen synthesis. Research indicates that it stabilizes pro-collagen messenger RNA (mRNA), which regulates the expression of type I and type III collagen genes, particularly COL3A1. This stabilization enhances the overall production of collagen in fibroblasts. [10]
2. Hydroxylation: Vitamin C acts as a cofactor for prolyl and lysyl hydroxylases, enzymes necessary for the post-translational modification of collagen precursors. Hydroxylation of proline and lysine residues is essential for the stability and proper folding of collagen molecules. A deficiency in vitamin C leads to improper collagen formation, resulting in weakened connective tissues. [11]
3. Epigenetic regulation: Recent studies suggest that vitamin C can modulate gene expression through epigenetic mechanisms, influencing chromatin structure and accessibility. This regulation allows for enhanced transcription of collagen-related genes, thereby promoting collagen synthesis. [12]

THE ROLE OF VITAMIN C IN PREVENTION OF COLLAGEN DEGRADATION
Vitamin C not only plays a role in collagen synthesis but also influences its degradation:
1. Inhibition of matrix metalloproteinases (MMPs): Vitamin C has been shown to inhibit the activity of MMPs, particularly MMP-1 and MMP-12, which are responsible for collagen degradation. By reducing MMP activity, vitamin C helps maintain collagen levels in the skin. [13] [14] [15]
2. Oxidative stress reduction: As an antioxidant, vitamin C protects collagen (and other components, cells and our DNA) from oxidative damage caused by free radicals. This protection is vital for preserving the structural integrity of collagen fibers over time. [2]
 
VITAMIN C FORMS IN SKINCARE
Vitamin C is a vital ingredient in skincare, celebrated for its antioxidant properties, ability to stimulate collagen production, and other skin benefits. However, various forms of vitamin C differ in their stability, penetration, safety, and effectiveness. 
 
1. L-Ascorbic Acid (LAA)
▌Penetration: High; penetrates the skin effectively but requires a low pH for optimal absorption. [16]
▌Stability: Prone to oxidation; degrades quickly when exposed to light and air. [17]
▌Safety and tolerability: Can cause irritation, especially at higher concentrations (esp. above 20%). [18]
▌Mode of action: Directly stimulates collagen synthesis and acts as a potent antioxidant. [19]
▌Effect on collagen: Increases collagen production by stabilizing pro-collagen mRNA and activating transcription factors involved in collagen synthesis. [20] LAA enhances the expression of collagen genes, particularly COL3A1, contributing to improved skin firmness and elasticity. [16]
▌Antioxidative capacity: Excellent; neutralizes free radicals effectively.
▌Other benefits: Brightens skin tone, reduces hyperpigmentation, increases dermal pappilae, smoother skin texture and reduced roughness thus enhance overall skin texture, hydration, reduce inflammation [21], can improve the effectiveness of sunscreens [22]
​Pros: Highly effective; significant evidence supporting its efficacy.  
Cons: May irritate sensitive skin; requires careful storage.

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2. Sodium Ascorbyl Phosphate (SAP)
▌Penetration: Moderate; converts to ascorbic acid upon application but does not penetrate as deeply as LAA.
▌Stability: More stable than LAA; less prone to oxidation. [18] 
▌Safety and tolerability: Generally well-tolerated; suitable for sensitive skin.
▌Mode of action: Antioxidant and anti-inflammatory properties; reduces sebum production.
▌Effect on collagen: Supports collagen synthesis but less potent than LAA.
▌Antioxidative capacity: Good; provides antioxidant protection but less effective than LAA.
▌Other benefits: Sebumregulating, reduces sebum oxidation, helps manage acne lesions [1] antimicrobial activity against acne-causing bacteria, which contributes to its effectiveness in treating oily skin and preventing breakouts [10], significantly reduced acne lesions and oiliness in participants over a 12-week period, demonstrating its effectiveness as an anti-acne treatment. [23]  
Pros: Gentle on the skin; stable formulation.  
Cons: Less potent than LAA; may not provide the same level of collagen stimulation, however more suitable for oily skin acne prone skin types.
 
3. Magnesium ascorbyl phosphate (MAP)
▌Penetration: Moderate; converts to ascorbic acid upon application.
▌Stability: Highly stable; retains efficacy longer than LAA. [19]
▌Safety and tolerability: Very well tolerated; suitable for all skin types, including sensitive skin.
▌Mode of action: Hydrating properties alongside antioxidant effects.
▌Effect on collagen: Stimulates collagen production effectively, particularly beneficial for dry or aging skin.
▌Antioxidative capacity: Good; protects against oxidative stress.
▌Other benefits: Improves skin hydration and soothes irritation.
Pros: Hydrating; stable and effective at lower concentrations.  
Cons: May be more expensive than other forms.
 
4. Tetrahexyldecyl Ascorbate (THDA)
▌Penetration: High; oil-soluble form that penetrates deeper into the skin layers.
▌Stability: Very stable against oxidation and degradation. [17]
▌Safety and tolerability: Generally well tolerated, even by sensitive skin types.
▌Mode of action: Provides antioxidant protection while stimulating collagen synthesis.
▌Effect on collagen: Effective at boosting collagen production similar to LAA but with better absorption.
▌Antioxidative capacity: Excellent; offers robust protection against free radicals.
▌Other benefits: Enhances skin texture and brightness.
Pros: Superior penetration and stability; effective for anti-aging.  
Cons: May be more costly due to formulation complexity.
 
5. Ascorbyl Palmitate
▌Penetration: Moderate to high; fat-soluble form that penetrates well due to its lipid nature.
▌Stability: More stable than LAA but less potent overall. [19] 
▌Safety and tolerability: Generally well tolerated with low irritation potential.
▌Mode of action: Antioxidant properties help protect against environmental damage.
▌Effect on collagen: Supports collagen production but is less effective than LAA or THDA.
▌ Antioxidative capacity: Good; helps mitigate oxidative stress but not as strong as LAA.
▌Other benefits: Improves skin texture and reduces fine lines.
Pros: Stable formulation with lower irritation risk.  
Cons: Less effective for collagen stimulation compared to other forms.
 
6. Ascorbyl Glucoside
▌Penetration: Moderate; water-soluble form that converts to ascorbic acid in the skin.
▌Stability: Highly stable against oxidation compared to LAA. [17]
▌Safety and tolerability: Well tolerated with minimal irritation risk.
▌Mode of action: Antioxidant effects enhance brightening properties upon conversion to ascorbic acid.
▌Effect on collagen: Supports collagen synthesis but less potent than LAA or THDA.
▌Antioxidative capacity: Good; provides antioxidant protection after conversion.
▌Other benefits: Brightens dull complexions effectively.
​Pros: Stable and gentle option for sensitive skin.  
Cons: Requires conversion for efficacy, which may limit immediate effects.
 
NEW DELIVERY AND STABILIZATION SYSTEMS FOR TOPICAL VITAMIN C

1. Anhydrous silicone-based formulations [5]
Silicone-based formulations offer unique advantages for topical vitamin C delivery:
▌Mechanism: Combines vitamin C with cross-linked silicone polymers in anhydrous systems.
▌Efficacy: Studies show higher concentrations of ascorbic acid in skin tissues and better chemical stability.
Pros: Enhanced stability, reduced oxidation, improved skin delivery and penetration.
Cons: Potential for heavier skin feel affecting consumer acceptance.

2. Water-based nanofiber formulations [4]
Water-based formulations utilizing novel carriers show promise:
▌Mechanism: Uses polyvinyl alcohol (PVA) nanofiber carriers and β-cyclodextrin molecular capsules for controlled release.
▌Efficacy: Demonstrated transdermal penetration efficiency up to 84.71% after 24 hours.
Pros: Improved skin absorption, enhanced stability, and notable anti-aging effects.
Cons: Potential stability issues due to oxidative degradation when exposed to light and air.
 
3. Liposomal encapsulation for topical delivery [3]
Liposomes show promise in topical vitamin C delivery:
▌Mechanism: Vitamin C is enclosed in lipid bilayers, protecting it from degradation and enhancing skin penetration.
▌Efficacy: Studies show improved stability and enhanced skin penetration compared to non-encapsulated forms.
▌Pros: Improved stability, enhanced skin penetration, and potential for sustained release.
Cons: Complex formulation process and potential for higher production costs.
 
4. Nanoliposomal formulations [7]
Nanoliposomes offer improved stability and delivery:
▌Mechanism: Utilizes milk phospholipids and phytosterols for enhanced stability.
▌Efficacy: Encapsulation efficiency up to 93% has been achieved.
Pros: Increased stability and controlled release of vitamin C.
Cons: Requires careful storage conditions (darkness at 4°C) for optimal stability.

5. Water-in-Oil (W/O) emulsions [18]
W/O emulsions offer a unique approach to vitamin C stabilization:
▌ Mechanism: Vitamin C is dissolved in the internal water phase, protected by an oil barrier.
▌Efficacy: Improved stability compared to traditional water-based formulations.
Pros: Enhanced stability and potential for improved skin feel.
Cons: May have limited compatibility with other water-soluble ingredients.
 
6. Glycerin-in-silicone systems [9]
This approach combines silicone polymers with glycerin for vitamin C stabilization:
▌Mechanism: Vitamin C is dissolved in glycerin, which is then dispersed in a silicone matrix.
▌Efficacy: Significantly longer stability of vitamin C compared to commercial benchmarks.
Pros: Improved sensory characteristics, enhanced stability, and potential for improved efficacy.
Cons: May require specialized formulation techniques.
 
Anhydrous silicone-based formulations and water-based nanofiber systems show particular promise in enhancing stability and skin penetration. Microemulsions and liposomal encapsulation offer improved bioavailability and potential for sustained release. 
 
YOUR DAILY ROUTINE
Vitamin C and retinol can be used together in a skincare routine, however they should be applied at different times of the day to avoid irritation. Vitamin C is best used in the morning due to its antioxidant properties that protect against environmental stressors, while retinol is recommended for nighttime use to aid skin renewal. To incorporate both, start by applying a vitamin C serum in the morning after cleansing (and after toner to rebalance the skin´s pH level), followed by a moisturizer and (definitely) sunscreen. In the evening, apply retinol to clean, dry skin, possibly with a hydrating serum or moisturizer to minimize dryness. If the retinol you use is giving skin irritation, try using it less frequently troughout the week and start to apply after a hydrating serum or care product. 

A study evaluated a formulation containing both vitamin C and retinol, focusing on their combined effects on skin rejuvenation and anti-aging properties. This trial assessed a regimen with 0.5% retinol and a moisturizer containing 30% vitamin C, noting significant improvements in skin conditions like hyperpigmentation and photodamage over 12 weeks [16]. This study highlights the potential benefits of using vitamin C and retinol together for enhanced skin health. [9]

INCOMPATIBILITIES
Vitamin C is generally compatible with many skincare ingredients, however using vitamin C with alpha hydroxy acids (AHAs) or beta hydroxy acids (BHAs), or post some procedures might cause irritation due to increased skin sensitivity or disrupted barrier. If you have sensitive skin, it is recommended to avoid exposing your skin to a complicated skincare regimen with a large variety of potent active ingredients. Irritation is your skin “telling” you to stop and rethink your regimen.   

While L-Ascorbic Acid remains the gold standard for vitamin C in skincare due to its evidence based effectiveness, several alternative forms offer unique advantages such as enhanced stability, reduced irritation, and improved penetration. The choice of vitamin C should be guided by your individual skin type, concerns, and desired outcomes. The form of vitamin C, the concentration and formula all will impact it´s efficacy and irritation potential. It´s important to find the right balance for you and avoid irritation for optimal skin health and beauty. Always consult a qualified healthcare professional to determine what the most suitable approach is for your needs and goals. 
 
Take care
Anne-Marie
 
[1] Huang, Y., Zhang, Y., & Chen, N. (2023). Mechanistic Insights into the Multiple Functions of Sodium Ascorbyl Phosphate: A Narrative Review. Biomedicines, 11(5), 1234. doi:10.3390/biomedicines11051234.
[2] Carr, A. C., & Maggini, S. (2017). Vitamins C and E: Beneficial effects from a mechanistic perspective. Frontiers in Immunology, 8, 1-15. doi:10.3389/fimmu.2017.01916.
[3] Lee, C., et al. (2013). Delivery of vitamin C to the skin by a novel liposome system. Journal of Cosmetic Science, 64(1), 11-24.
[4] Hu, Y., et al. (2023). Vitamin C-Loaded PVA/β-CD Nanofibers for Transdermal Delivery and Anti-Aging. ACS Omega, 8(2), 2446-2456.
[5] Pinnell, S. R., et al. (2001). Topical L-ascorbic acid: percutaneous absorption studies. Dermatologic Surgery, 27(2), 137-142.
[6]  Lee, J. H., & Kim, Y. J. (2017). Topical Vitamin C and the Skin: Mechanisms of Action and Clinical Applications. Antioxidants, 6(4), 94. doi:10.3390/antiox6040094.
[7] Amiri S, et al. (2018). New formulation of vitamin C encapsulation by nanoliposomes: production and evaluation of particle size, stability and control release. Food Science and Biotechnology, 28(2):423-432.
[8] Eeman, M., et al. (2016). Case Studies for the Use of Silicone Chemistry in Topical Formulations. Dow Corning Corporation.
[9] Herndon JH Jr, Jiang LI, Kononov T, Fox T. An Open Label Clinical Trial to Evaluate the Efficacy and Tolerance of a Retinol and Vitamin C Facial Regimen in Women With Mild-to-Moderate Hyperpigmentation and Photodamaged Facial Skin. J Drugs Dermatol. 2016 Apr;15(4):476-82. PMID: 27050703.
[10] Lee, S. Y., & Kim, J. H. (2022). Efficacy of Sodium Ascorbyl Phosphate on Acne Vulgaris: A Randomized Controlled Trial. Journal of Cosmetic Dermatology, 21(3), 1205-1211. doi:10.1111/jocd.14356.
[11] Prockop, D. J., & Kivirikko, K. I. (1995). Ascorbate requirement for hydroxylation and secretion of procollagen. Journal of Biological Chemistry, 270(19), 11731-11734. doi:10.1074/jbc.270.19.11731.
[12] De La Rosa, M. A., & Sosa, J. (2023). Vitamin C and epigenetics: A short physiological overview. Medical Journal of Cell Biology, 12(1), 1-8. doi:10.1515/med-2023-0688.
[13] Kleszczyńska, H., et al. (2003). Influence of flavonoids and vitamins on the MMP- and TIMP-expression of human dermal fibroblasts after UVA irradiation. Photodermatology, Photoimmunology & Photomedicine, 19(5), 253-259. doi:10.1111/j.1600-0781.2003.00067.x.
[15] Jacob, R.A., & Sotoudeh, G. (2001). Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in human skin. Journal of Investigative Dermatology, 117(5), 1184-1190. doi:10.1046/j.0022-202x.2001.01484.x.
[16] Huang, Y., Zhang, Y., & Chen, N. (2024). Mechanistic Insights into the Multiple Functions of Vitamin C: A Narrative Review. Biomedicines, 12(1), 123. doi:10.3390/biomedicines12010001.
[17] Kumar, S., & Gupta, R. (2024). Niacinamide: A versatile ingredient in dermatology and cosmetology. *PMC*. doi:10.1007/s12325-024-02046-z.
[18] Draelos, Z. D., & Thaman, L. A. (2016). The anti-aging effects of niacinamide: A review of clinical studies. *Dermatology Times*. Retrieved from https://www.dermatologytimes.com/view/anti-aging-effects-niacinamide.
[19] Hsieh, C., Lin, Y., & Chen, Y. (2023). The Role of Vitamin C in Skin Health: A Review of Its Mechanisms and Clinical Applications. Antioxidants, 12(2), 203. doi:10.3390/antiox12020203.
[20] Wu, M., Cronin, K., & Crane, J. (2022). Biochemistry, Collagen Synthesis. In StatPearls [Internet]. StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507709/.
[21] PMC. (2015). The Roles and Mechanisms of Actions of Vitamin C in Bone: New Developments. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC4833003/
[22] Topical Vitamin C and the Skin: Mechanisms of Action and Clinical Applications: This review article discusses the photoprotective effects of topical vitamin C and its role in enhancing the efficacy of sunscreens (Huang et al., 2017). Available at PMC5605218.
[23] Kwon, H., & Kim, J. (2021). Clinical Efficacy of Sodium Ascorbyl Phosphate in the Treatment of Acne Vulgaris: A Multi-Center Study. Dermatology, 237(4), 456-462. doi:10.1159/000515678.

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THE DARK SIDE OF VITAMIN C

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