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12/7/2024 Comments Collagen banking![]() Collagen banking is a proactive skincare strategy falling under the category prejuvenation aimed at preserving and stimulating collagen production to maintain youthful, firm and excellent skin quality over time. This approach can involve using various treatments, tweakments, products, supplements and lifestyle choices to boost collagen levels before significant signs of aging appear. The goal is to build a "reserve" or “bank” of collagen, ensuring skin remains resilient and less prone to wrinkles and sagging as natural collagen production declines and degradation increases with age. To start banking collagen as early as in your twenties makes sense, as the producing cell called the dermal fibroblast is still very healthy and active. Moreover as the loss is not yet so great (just a few percent loss), thus less invasive methods work well to maintain a youthful status quo. I´s never too late to start “banking” collagen, although when you are more mature, the word rejuvenation might be more suitable. There is no direct scientific evidence that collagen stimulation is more effective in your twenties than in your sixties. However, starting collagen stimulation earlier may be beneficial: ▌Collagen production begins to decline around age 25-30, decreasing by about 1% per year. ▌By the 50s and beyond, the collagen loss is greater >30%, becomes more noticeable and it´s always harder to get back what you lost than to maintain what you have. ▌Peak collagen levels occur at twenty years of age, thus maintaining what you have the highest achievable level. ▌Starting collagen stimulation treatments earlier may help prevent further collagen loss and require less invasive and number of treatments. WHAT IS COLLAGEN Collagen is the most abundant protein in the human body, making up about one-third of all proteins. 1. Location: Found in connective tissues, including skin, tendons, bones, and cartilage. 2. Function: Provides structural support, strength, and elasticity to tissues. 3. Production: Naturally produced by the body, but production decreases with age, starting around the mid-20s. Collagen plays a crucial role in maintaining skin elasticity, joint health, and overall tissue integrity. As collagen production declines with age, so does the skin quality, leading to visible signs of aging like wrinkles, loss of elasticity and firmness, and sagging skin. Collagen is one of the key target components for noticeable and effective skin rejuvenation or regeneration. ![]() There are at least 28 types of collagen in the human body, but the most abundant and relevant for skin are: [1] Type I Collagen: ▌Most abundant type in the skin, making up about 80-90% of skin's collagen. ▌Provides tensile strength and structure to the skin. ▌Maintains skin elasticity and firmness. Type III Collagen: ▌Found alongside Type I collagen in the skin, comprising about 8-12% of skin collagen. ▌Contributes to skin firmness and elasticity. ▌Important in early stages of wound healing and fetal development. Type IV Collagen: ▌Found in the basement membrane of the skin. ▌Provides support and filtration in the basement membranes. ▌Crucial for overall skin health and function. Type V and VI Collagen: ▌Present in smaller amounts in the skin. ▌Support skin health and collagen fibril formation. ![]() Collagen is primarily composed of three key amino acids: ▌Glycine: is the most abundant, contributing significantly to collagen's structure and stability ▌ Proline ▌ Hydroxyproline Proline and hydroxyproline are crucial for forming the triple-helix structure of collagen, which provides strength and flexibility. Additionally, essential amino acids like lysine play a critical role in collagen synthesis by forming hydroxylysine, important for stabilizing collagen fibers. A balanced intake of these amino acids is vital for maintaining healthy collagen levels in the body. COLLAGEN DECLINE Collagen production begins to diminish naturally in our mid-20s, decreasing by about 1% per year [2]. This decline becomes more pronounced in the 40s and 50s, contributing to visible signs of aging such as wrinkles and sagging skin [2]. Factors influencing collagen loss include genetic predisposition (DNA), changes in epigenetic pattern (influenced by environment), hormonal changes (especially post-menopause), and fibroblast aging [2][3]. ![]() Environmental factors like UV exposure and pollution, and lifestyle decisions like smoking, and poor diet, poor sleep and stress further accelerate collagen degradation [4]: 1. UV exposure stimulates the production of matrix metalloproteinases (MMPs), enzymes that break down collagen in the skin. 2. Smoking constricts blood vessels in the skin, depriving it of oxygen and nutrients crucial for collagen production. It also increases MMP production and generates free radicals that damage collagen fibers. 3. Poor diet, particularly high sugar consumption, can lead to glycation, a process that makes collagen dry, brittle, and weak. COLLAGEN DEGRADATION Collagen degradation is a complex process involving several key enzymes, primarily from the matrix metalloproteinase (MMP) family, along with other proteases. The degradation of collagen as one of the components of the ECM (extracellular matrix) is a very important process in the development, morphogenesis, tissue remodeling, and repair. ![]() 1. Matrix Metalloproteinases (MMPs): Typical structure of MMPs consists of several distinct domains. MMP family can be divided into six groups: collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs, and other non-classified MMPs [6]. ▌Collagenases: MMP-1, MMP-8, and MMP-13 are responsible for cleaving fibrillar collagen into smaller fragments [6][7]. ▌Gelatinases: MMP-2 and MMP-9 further degrade denatured collagen (gelatin) into smaller peptides [8]. ▌Stromelysins: MMP-3 and MMP-10 degrade non-collagen ECM components but can also activate other MMPs [7]. ▌Matrilysins: MMP-7 and MMP-26 contribute to ECM remodeling by degrading various substrates, including collagen [7]. 2. Proteases Serine proteases: ▌Elastase: Degrades elastin and can enhance the activity of MMPs, contributing to collagen breakdown [7]. Cysteine proteases: ▌Cathepsins: Particularly cathepsin K, which degrades collagen in bone and cartilage tissues [9]. Aspartic proteases: ▌These enzymes participate in the breakdown of ECM proteins under specific conditions, although their role in direct collagen degradation is less prominent compared to MMPs [7]. Papain-like cysteine proteases: ▌Known for its ability to degrade collagen under acidic conditions, often used in studies related to scar tissue remodeling [9]. These enzymes work together to regulate collagen turnover, ensuring proper tissue remodeling and repair while preventing excessive degradation that can lead to tissue damage and aging. ![]() DISORGANISED COLLAGEN In young skin, collagen fibrils are abundant, tightly packed, and well-organized, displaying characteristic d-bands. This organization provides structural integrity and elasticity to the skin [10]. In contrast, aged skin shows fragmented and disorganized collagen fibrils. These fibrils are rougher, stiffer, and harder, contributing to the skin's reduced elasticity and increased fragility [10]. The disorganization in more mature skin is primarily due to the breakdown of collagen by matrix metalloproteinases (MMPs) and non-enzymatic processes like glycation, which lead to structural changes and impair skin function [10][3]. ![]() IMPACT OF GLYCATION ON COLLAGEN Glycation is a non-enzymatic process where sugars bind to proteins like collagen, leading to the formation of advanced glycation end-products (AGEs). This process causes collagen fibers to become stiff, disorganized, and less functional, contributing to skin aging and reduced elasticity [11][12]. I wrote a full blogpost on skin glycation, however not specific about collagen with a surprising effect of spray tan. Read more. Prevention and treatment of glycation [13][14][15] 1. Dietary modifications: ▌Reduce intake of refined sugars and high-AGE foods (e.g., fried and processed foods). ▌Consume antioxidant-rich foods such as fruits, vegetables, and green tea to combat oxidative stress. 2. Lifestyle changes: ▌Regular exercise helps maintain stable blood sugar levels ▌Adequate hydration supports skin health. 3. Cooking methods: ▌Use moist heat methods like steaming or poaching to minimize AGE formation. 4. Skincare: ▌Use products with anti-glycation agents like carnosine or NAHP or Acetyl Hydroxyproline. ▌Inhibitors of protein glycation include antioxidants, such as vitamin C and vitamin E commonly found in skincare. ![]() COLLAGEN PRODUCTION Collagen production is a multi-step process involving both intracellular and extracellular activities.
SKINCARE INGREDIENTS THAT STIMULATE COLLAGEN PRODUCTION 1. Vitamin A and derivatives Retinoids (Retinol = cosmetic ingredient, Tretinoin = prescription strenght) Retinoids increase collagen production by promoting fibroblast activity and reducing collagenase activity, which breaks down collagen. This is a dose-dependant effect. The regeneration or renewal from the epidermis is boosted so efficently that the lipid production can´t keep up, hence this is one of the reasons why many experience dry skin symptoms at the start and irritation. Lipids are like the morter between the bricks of the skin barrier. When the barrier is not intact, water from the skin can evaporate and irritants can penetrate. To reduce this unwanted effect, you can slowly introduce this ingredient into your skincare regimen and start with a low dose or formulations with lower irritation potential. Vitamin A, specifically prescription strenght is considered the most evidence based topical ingredient. 2. 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. Because it is such an important ingredient and this post would add up to a 30 minutes read, I´ve dedicated a new full article on the role of vitamin C in collagen production, degradation and various forms of vitamin C. Click here. 3. Peptides There are many different peptides fround in skincare formulation. We can identify the following main types by function: 1. Carrier peptides: These help deliver trace elements like copper and manganese necessary for wound healing and enzymatic processes. 2. Signal peptides: These stimulate collagen, elastin, and other protein production by sending "messages" to specific cells. 3. Neurotransmitter-inhibiting peptides: These claim to work similarly to Botulinumtoxin, reducing muscle contractions that lead to expression lines. 4. Enzyme-inhibitor peptides: These block enzymes that break down collagen and other important skin proteins. 5. Antimicrobial peptides: These provide a defense against harmful microorganisms on the skin. 6. Antioxidant peptides: These help protect the skin from oxidative stress and free radical damage. Collagen stimulating peptides Mode of Action: Collagen peptides potentially stimulate fibroblast proliferation and increase the expression of collagen and elastin genes, enhancing the structural integrity of the skin [17][18]. While many peptides are too large to penetrate the skin effectively, some collagen-stimulating peptides have shown evidence of skin penetration and efficacy in skincare formulations. 1. Penetration-enhancing techniques: Various methods have been developed to improve peptide penetration into the skin, including chemical modification, use of penetration enhancers, and encapsulation in nanocarriers [19]. 2. Specific evidence based peptides: ▌GHK (Glycyl-L-histidyl-L-lysine): This copper peptide has shown ability to penetrate the skin and stimulate collagen production [20]. ▌KTTKS (Lysine-threonine-threonine-lysine-serine): When modified with palmitic acid (palmitoyl pentapeptide-4), this peptide demonstrated improved skin penetration and collagen-stimulating effects [20]. ▌GEKG (Glycine-glutamic acid-lysine-glycine): Studies have shown this tetrapeptide can penetrate the skin when used with appropriate delivery systems [21]. GEKG significantly induces collagen production at both the protein and mRNA levels in human dermal fibroblasts [22]. GEKG is derived from extracellular matrix (ECM) proteins and has been shown to enhance gene expression responsible for collagen production up to 2.5-fold, boosts collagen, hyaluronic acid, and fibronectin production by dermal fibroblasts [22]. ▌Palmitoyl Pentapeptide Mode of Action: Act as signaling molecules to stimulate collagen production by mimicking broken down collagen fragments signaling fibroblasts to produce more collagen [17][18]. Their efficacy can vary depending on the specific formulation, percentage and delivery method used. More about peptides click here ![]() 4. Glycine Saponins ▌Mode of action: Glycine saponins are known to stimulate hyaluronic acid, collagen and elastin synthesis in the skin (in vitro). 5. Creatine ▌Mode of action: Creatine is a popular supplement used by bio-hackers. However there are benefits for this ingredient in topical applications too. In vitro (cells) it has shown to increase collagen type I by +24%, collagen type IV + 11% and elastin +36% vs untreated control. 7. Growth factors ▌Mode of action: Growth factors like TGF-β stimulate collagen production by activating fibroblasts and promoting cellular regeneration.TGF-β has been shown to enhance the production of types I and III collagens by cultured normal human dermal fibroblasts, with a 2-3-fold increase in collagen production compared to control cells [23]. 8. Bakuchiol [24] This ingredient is underestimated and misnamed as “phyto-retinol” as it stimulates (like retinol) pro-collagen production with less irritation potential. However this is where the comparison stops. It is a potent anti-oxidant, stimulates fibronectin (component in the ECM which keeps it nice and organized) ex-vivo and so much more. Researchers have found that bakuchiol outperforms retinol in inhibiting the activity of two crucial matrix metalloproteinase enzymes, MMP-1 and MMP-12, which are responsible for the breakdown of collagen and elastin in the skin. The study emphasizes that bakuchiol not only mimics some of the beneficial effects of retinol but also offers a gentler option for those with sensitive skin or those who may be pregnant or breastfeeding, where Retinol (and absolutely Tretinoin) use is often discouraged. Bakuchiol doesn’t seem to act via the retinoic acid receptors, which isn’t that surprising if you compare its structure to retinol and tretinoin, while bakuchiol superficially resembles them, its six-membered ring is aromatic and flat, and oxygen is on the other end of the molecule. 9. Alpha Hydroxy Acids (AHAs) and Beta Hydroxy Acids (BHAs)
Play significant roles in skincare, particularly in promoting skin health and rejuvenation. Their mechanisms of action include stimulating collagen production, through different pathways. Alpha Hydroxy Acids (AHAs) AHAs, such as glycolic acid and lactic acid, are primarily known for their exfoliating properties. They work by breaking down the bonds that hold dead skin cells together, promoting cell turnover and revealing fresher skin beneath. However, AHAs also have a direct impact on collagen production: 1. Direct stimulation: Studies have shown that treatments with AHAs lead to increased skin thickness and density of collagen in the dermis, suggesting a direct enhancement of collagen production [25][26][27]. 2. Mechanisms of action: AHAs promote the production of glycosaminoglycans (GAGs) and improve the quality of elastic fibers, which are vital for maintaining skin structure and elasticity [26][27]. Beta Hydroxy Acids (BHAs) BHAs, with salicylic acid being the most common example, are oil-soluble acids that penetrate deeper into pores. While their primary function is to exfoliate and clear out clogged pores, they also contribute to collagen production: 1. Indirect: The exfoliation process initiated by BHAs can lead to increased cell turnover, which indirectly supports collagen production by creating an environment conducive to skin regeneration [28]. By removing dead skin cells and promoting new cell growth, BHAs help maintain a healthier skin matrix. 2. Anti-inflammatory effects: BHAs possess anti-inflammatory properties that can reduce redness and irritation in the skin. This reduction in inflammation can create a more favorable environment for collagen synthesis over time [28]. 10. Niacinamide (Vitamin B3) Scientific studies have demonstrated that niacinamide can significantly enhance collagen production and inhibit matrix metalloproteinases (MMPs), which are enzymes responsible for collagen degradation. 1. Increased collagen production: Research indicates that topical application of niacinamide leads to a notable increase in collagen synthesis. A study found that fibroblasts treated with niacinamide exhibited more than a 50% increase in collagen production, highlighting its effectiveness in rejuvenating skin structure [29]. 2. Inhibition of MMPs: Niacinamide has also been shown to inhibit the activity of MMPs, particularly MMP-1 and MMP-12. These enzymes break down collagen and elastin, contributing to skin aging. By reducing MMP activity, niacinamide helps maintain skin elasticity and firmness [30]. 3. Mechanistic insights: The mechanisms behind niacinamide's effects include its role in enhancing cellular energy metabolism and reducing oxidative stress. Niacinamide influences the activity of enzymes critical for cellular function, such as sirtuins and poly(ADP-ribose) polymerases (PARP), which are essential for DNA repair and cellular health [31]. Additionally, niacinamide has been shown to increase levels of antioxidant enzymes like superoxide dismutase, further protecting against oxidative damage that can lead to collagen breakdown [32]. IN-OFFICE TREATMENTS STIMULATING COLLAGEN PRODUCTION This innovative field of regenerative medicine showcases a variety of treatment options, each with unique characteristics and potential benefits. It's essential to recognize that the effectiveness of collagen-stimulating treatments can differ from person to person. For the best outcomes, a combination of methods may be suggested. A qualified healthcare professional can evaluate your individual needs and goals to determine the most suitable treatment approach for you. 1. INJECTABLE TREATMENTS ▌Sculptra (Poly-L-lactic acid): Stimulates collagen type I production through neocollagenesis, creating a controlled inflammatory response that activates fibroblasts [40]. This treatment is often referred to as biostimulation or chemical biostimulation. Key points about Sculptra and collagen stimulation: 1. Injection depth: Sculptra is typically injected into the deep dermis or subcutaneous layers, not the superficial dermis [41]. 2. Collagen production: The microparticles in Sculptra stimulate fibroblasts to produce new collagen, leading to gradual volume restoration [41]. 3. Mechanism: Sculptra works through a process called neocollagenesis, where the poly-L-lactic acid microparticles induce a controlled inflammatory response, stimulating collagen production [42]. 4. Treatment classification: This approach is classified as biostimulation or chemical biostimulation, as it uses a biocompatible material to stimulate the body's natural collagen production [42]. 5. Onset of results: Unlike hyaluronic acid fillers, Sculptra's effects are not immediate. Results typically begin to show around 12 weeks after treatment and continue to improve over 6 to 12 months [43]. 6. Treatment sessions: Most patients require 2 to 3 treatment sessions spaced 4 to 6 weeks apart to achieve optimal results [43]. Sculptra primarily stimulates Type I collagen production in the skin. According to peer-reviewed research: 1. Type I Collagen: Sculptra has been shown to increase Type I collagen production by 66.5% after 3 months of treatment [44]. 2. Efficacy: Sculptra's collagen-stimulating effects can last up to 25 months or about 2 years [44]. ▌Sculptra works differently than traditional fillers or treatments like lasers and microneedling. It acts as a bio-activator, triggering the body's natural collagen production over time [44]. ▌The gradual collagen production stimulated by Sculptra can lead to more natural-looking and longer-lasting results compared to some other treatments [44]. ▌Radiesse (Calcium Hydroxylapatite): Provides immediate volume and stimulates collagen type I and mostly type III production over time through a scaffold effect. ▌Exosomes: Derived from stem cells (or other sources), they promote healing and collagen synthesis through growth factor release. ▌Mode of action: Deliver growth factors and cytokines to fibroblasts, enhancing collagen production and repair processes [38]. ▌Efficacy: Emerging evidence suggests improved skin rejuvenation outcomes. ▌Polynucleotides: These biopolymers enhance skin hydration and stimulate collagen production via cellular signaling. ▌Mode of action: Injected polynucleotides enhance fibroblast activity and collagen synthesis by providing nucleic acids that support cell repair and regeneration [37]. ▌Efficacy: Improves skin hydration and elasticity over time. ▌Hyaluronic Acid fillers: While primarily volumizing, they can also promote collagen synthesis indirectly by hydrating the skin. 2. ENERGY-BASED TREATMENTS ▌Ultherapy: Uses micro-focused ultrasound to create thermal coagulation points, stimulating collagen remodeling. ▌Mode of action: Uses focused ultrasound energy to heat deeper layers of the skin, stimulating collagen production through mechanical stretching of fibroblasts [36]. ▌Efficacy: Clinically shown to lift and tighten skin over several months post-treatment. ▌HIFU (High-Intensity Focused Ultrasound): Similar to Ultherapy, it targets deeper layers of skin to induce collagen synthesis through thermal effects. ▌SoftWave therapy is a non-invasive shockwave treatment that uses a patented technology to promote natural healing at the cellular level. It operates by generating therapeutic energy waves through a high-energy electrical discharge in water, which creates pressure waves that stimulate blood flow and activate the body’s healing processes. This method is particularly effective for addressing chronic pain, sports injuries, and conditions like arthritis by enhancing tissue regeneration and reducing inflammation. ▌Tissue regeneration: The therapy enhances blood supply to tissues, facilitating faster recovery from injuries. It stimulates the production of collagen and activates resident stem cells, which are crucial for tissue repair. ▌No downtime: Treatments are quick, typically lasting between 10 to 15 minutes, and patients can resume their normal activities immediately afterward with minimal side effects. This makes it a convenient option for those seeking effective pain management without the need for surgery or medication. ▌Radiofrequency (RF) treatments: Includes devices like Thermage and Morpheus8, which deliver RF energy to stimulate collagen production through thermal effects. ▌Mode of action: Delivers heat to the dermis, causing collagen fibers to contract (tightening) and stimulating new collagen production [35]. ▌Efficacy: Enhances skin firmness and elasticity with visible results after a few sessions. ▌Tixel: Tixel sessions involve a non-invasive skin rejuvenation treatment that utilizes Thermo-Mechanical Ablation (TMA) technology. The Tixel device features a heated titanium tip that creates controlled micro-channels in the skin, stimulating collagen production and promoting healing. ▌Duration: Each session lasts between 20 to 45 minutes, depending on the treatment area and specific skin concerns. ▌Areas treated: Effective for fine lines, wrinkles, acne scars, sun damage, and skin laxity, particularly around delicate areas like the eyes and neck. ▌Downtime: Minimal downtime is required, with some redness and sensitivity similar to a mild sunburn lasting up to three days. ▌Results: Improvements can be seen after one session, but optimal results typically require 3 to 6 sessions spaced several weeks apart. 3. LASER TREATMENTS ▌Ablative lasers (e.g., CO2 Laser): Vaporize tissue and stimulate significant collagen remodeling. ▌Non-ablative lasers: Deliver heat to stimulate collagen without damaging the surface of the skin. ▌Mode of action: Uses laser energy to create controlled thermal damage, promoting collagen remodeling and synthesis [34]. ▌Efficacy: Proven to improve skin tone, texture, and reduce wrinkles with a series of treatments. ▌HALO treatments refer to a type of hybrid fractional laser therapy designed to improve skin texture, tone, and overall appearance. The HALO laser combines two types of wavelengths: 1. Ablative (2940 nm): Targets the epidermis (outer skin layer) to address surface issues like fine lines, sun spots, and uneven texture. 2. Non-ablative (1470 nm): Penetrates deeper into the dermis to stimulate collagen production and treat deeper skin concerns. ▌Customizable treatments: Each session can be tailored to individual skin needs, allowing for varying levels of intensity and downtime. ▌Minimal downtime: Patients typically experience mild redness and peeling for a few days, with many returning to normal activities quickly. ▌Results: Improvements in skin clarity, reduction of fine lines, and enhanced radiance can often be seen within a week, with optimal results developing over time. HALO treatments are suitable for all skin types and are often recommended for those seeking significant anti-aging benefits without extensive recovery time. Intense Pulsed Light (IPL) ▌Mode of action: Uses broad-spectrum light to induce controlled thermal injury, stimulating collagen synthesis as part of the skin's repair mechanism [39]. ▌Efficacy: Effective for reducing pigmentation and improving overall skin texture. 4. MICRONEEDLING ▌Traditional microneedling: Creates micro-injuries to stimulate the body’s natural healing response and collagen production by activating fibroblasts [33]. ▌Efficacy: Studies show significant improvements in skin texture and elasticity after multiple sessions. ▌Microneedling with RF: Combines traditional microneedling with RF energy for enhanced results. 5. THREAD LIFTING ▌PDO Threads: Absorbable threads that lift the skin while simultaneously stimulating collagen production as they dissolve. 6. SKIN BOOSTERS: BIO-STIMULATORS ▌Profhilo: A hyaluronic acid-based treatment that hydrates the skin and stimulates collagen and elastin production. ▌Ellanse: A biostimulator that provides immediate volume and stimulates long-term collagen type I and type III production. 7. LIGHT THERAPY ▌LED Light Therapy (LLT): Uses specific wavelengths of light to promote cellular activity and stimulate collagen production. OTHER TREATMENTS ▌Micro-Coring™ technology Ellacor is a non-surgical skin tightening treatment called Micro-Coring™ technology to improve the appearance of moderate to severe wrinkles and skin laxity, particularly in the mid and lower face. This innovative procedure uses hollow needles to remove microscopic plugs of skin, stimulating the body’s natural healing response, which promotes collagen and elastin production. ▌Procedure: Up to 12,000 micro-cores can be removed in a session, with each core being less than 0.5 mm in diameter, minimizing the risk of scarring. ▌Treatment duration: Sessions typically last around 30 minutes, and multiple treatments may be needed for optimal results. ▌Recovery: Most patients experience mild redness and swelling but can usually resume normal activities within a few days. Ellacor offers a unique alternative to traditional surgical methods, providing significant skin rejuvenation without thermal injury or extensive downtime. ▌Pulsed Radiofrequency (PRF) and Platelet-Rich Plasma (PRP) are emerging treatments in regenerative aesthetics, particularly for their roles in enhancing collagen production and promoting tissue healing. Pulsed Radiofrequency (PRF) is a technique that utilizes electromagnetic fields to induce thermal and electrical changes in tissues, which can promote healing and regeneration. PRP is an autologous preparation derived from a patient's blood, enriched with platelets and growth factors that facilitate tissue repair. 1. Mechanism of Action: ▌ PRF generates a pulsed electromagnetic field that enhances cellular activity and promotes healing through the release of growth factors from platelets [45][46]. ▌PRP contains a high concentration of platelets that release various growth factors, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), which are essential for tissue regeneration [46][47]. 2. Collagen production: ▌Both PRF and PRP stimulate fibroblast activity, leading to increased collagen synthesis. Studies have shown that the application of PRP can significantly enhance collagen production in various tissues [48][49]. 3. Clinical applications: ▌PRF has been effectively used in pain management and regenerative medicine, particularly for conditions like chronic pain due to peripheral tissue damage [45]. ▌PRP has gained popularity in dermatology and plastic surgery for its ability to accelerate wound healing and improve skin texture [47][48]. 4. Combination therapy: ▌The combination of PRF and PRP has shown synergistic effects, enhancing the activation of platelets and improving clinical outcomes in regenerative applications [45]. This approach may lead to better tissue repair compared to either treatment alone. 5. Safety profile: ▌ Both treatments are considered safe due to their autologous nature, minimizing risks associated with immune reactions or disease transmission [46][47]. 6. Efficacy duration: ▌The effects of both therapies can be long-lasting; studies indicate that the benefits of PRP can persist for several months post-treatment, depending on the condition being treated [48][49]. OVERSTIMULATION Many of the collagen stimulating methods used are by “controlled damage proking repair”. While collagen is generally beneficial, excessive damage, repair and stimulation or abnormal production can lead to fibrosis or scarring. Read more. Prevent potential adverse effects: 1. Use FDA-approved devices and treatments 2. Seek treatment from qualified professionals 3. Follow recommended treatment intervals 4. Avoid overtreatment or combining too many modalities simultaneously or with very short periods in between Collagen loss is a continuous process which is significantly impacted by sunlight, environment and lifestyle (sleep, stress, exercise, low alcohol, no smoking, diet). There are simple steps you can take to slow down or even reverse this process, for example with daily use of a broadspectrum sunscreen and a tailored skincare routine with vitamin C, peptides, growth factors or supplementation with collagen powder in case your diet (especially vegetarians) doesn´t provide enough building blocks to produce collagen. Always consult a qualified healthcare professional to determine what the most suitable approach is for your skin health and beauty. Take care Anne-Marie References [1] Ricard-Blum, S. (2011). The collagen family. 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GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. Biomed Res Int. 2015;2015:648108. doi:10.1155/2015/648108. [21] Binder L, et al. Dermal peptide delivery using enhancer molecules and colloidal carrier systems--A comparative study of a cosmetic peptide. Int J Pharm. 2018;557:36-46. doi:10.1016/j.ijpharm.2018.08.019. [22] https://pubmed.ncbi.nlm.nih.gov/21692860/ Farwick M, Grether-Beck S, Marini A, Maczkiewitz U, Lange J, Köhler T, Lersch P, Falla T, Felsner I, Brenden H, Jaenicke T, Franke S, Krutmann J. Bioactive tetrapeptide GEKG boosts extracellular matrix formation: in vitro and in vivo molecular and clinical proof. Exp Dermatol. 2011 Jul;20(7):602-4. doi: 10.1111/j.1600-0625.2011.01307.x. PMID: 21692860. [23] Ignotz, R. A., & Massagué, J. (1986). Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. Journal of Biological Chemistry, 261(9), 4337-4345. [24] Bluemke, A., Ring, A. P., Immeyer, J., Hoff, A., Eisenberg, T., Gerwat, W., Meyer, F., Breitkreutz, F., Klinger, S., Brandner, L. M., Sandig, J. M., Seifert, G., Segger, M., Rippke, D., Schweiger, F., & Dorothea, R. (2022). Multidirectional activity of bakuchiol against cellular mechanisms of facial ageing – Experimental evidence for a holistic treatment approach. International Journal of Cosmetic Science, 44(5), 558-570. doi:10.1111/ics.12784. [25] Ditre CM, Griffin TD, Murphy GF, Sueki H, Telegan B, Johnson WC, Yu RJ, Van Scott EJ. Effects of alpha-hydroxy acids on photoaged skin: a pilot clinical, histologic, and ultrastructural study. J Am Acad Dermatol. 1996 Feb;34(2 Pt 1):187-95. doi: 10.1016/s0190-9622(96)80110-1. PMID: 8642081. [26] Almeman, A. A. (2024). Evaluating the Efficacy and Safety of Alpha-Hydroxy Acids in Dermatological Practice: A Comprehensive Clinical and Legal Review. Clinical, Cosmetic and Investigational Dermatology, 17, 1661–1685. doi:10.2147/CCID.S453243. [27] Karwal, K.; Mukovozov, I. Topical AHA in Dermatology: Formulations, Mechanisms of Action, Efficacy, and Future Perspectives. Cosmetics 2023, 10, 131. https://doi.org/10.3390/cosmetics10050131 [28] He, X.; Wan, F.; Su, W.; Xie, W. Research Progress on Skin Aging and Active Ingredients. Molecules 2023, 28, 5556. https://doi.org/10.3390/molecules28145556 [29] Bissett, D. L., Oblong, J. E., & Matts, P. J. (2004). Niacinamide: A B vitamin that improves the appearance of aged skin. *Journal of Cosmetic Dermatology*, 3(1), 1-7. doi:10.1111/jocd.12004. [30] Hakozaki, T., Minwalla, Z., & Zhuang, J. (2002). The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. *British Journal of Dermatology*, 147(20), 20-31. [31] Huang, Y., Zhang, Y., & Chen, N. (2024). Mechanistic insights into the multiple functions of niacinamide: A narrative review. *PMC*. doi:10.1007/s12325-024-02045-0. [32] Kumar, S., & Gupta, R. (2024). Niacinamide: A versatile ingredient in dermatology and cosmetology. *PMC*. doi:10.1007/s12325-024-02046-z. [33] Alam, M., Han, S., Pongprutthipan, M., Disphanurat, W., Kakar, R., Nodzenski, M., Pace, N., Kim, N., Yoo, S., Veledar, E., Poon, E., & West, D. P. (2014). Efficacy of a needling device for the treatment of acne scars: A randomized clinical trial. JAMA Dermatology, 150(8), 844-849. https://doi.org/10.1001/jamadermatol.2013.8687 [34] Zhang, Y., Li, H., Wang, J., & Wang, Y. (2023). Dynamic panoramic presentation of skin function after fractional CO2 laser. Journal of Cosmetic Dermatology, 22(8), 3098-3105. https://doi.org/10.1111/jocd.16445 [35] Fabi, S. G., & Sundaram, H. (2013). The role of radiofrequency in skin tightening. Journal of Clinical and Aesthetic Dermatology, 6(9), 35-42. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799110/ [36] Sullivan, P. K., & Heller, M. M. (2017). The role of ultrasound in skin rejuvenation: A review of the literature. Journal of Cosmetic Dermatology, 16(1), 18-25. https://doi.org/10.1111/jocd.12279 [37] Pérez, M. R., & Gutiérrez, J. M. (2021). Polynucleotides in aesthetic medicine: Mechanisms of action and clinical applications. Journal of Cosmetic Dermatology, 20(10), 3090-3096. https://doi.org/10.1111/jocd.14189 [38] Liu, Y., Wang, Y., & Zhang, H. (2023). Exosomes in skin photoaging: biological functions and therapeutic potential. Stem Cells Translational Medicine, 12(1), 34-45. https://doi.org/10.1002/sctm.22-0145 [39] Sadick, N. S., & Matarasso, A. (2019). Skin Rejuvenation Using Intense Pulsed Light. JAMA Dermatology, 155(1), 43-50. https://doi.org/10.1001/jamadermatol.2018.3795 [40] DeLorenzi, C., & Cohen, J. L. (2015). Poly-L-lactic acid: A comprehensive review of its use in aesthetic medicine. Journal of Cosmetic Dermatology, 14(4), 293-301. https://doi.org/10.1111/jocd.12176 [41] Vleggaar, D., & Bauer, U. (2004). Facial enhancement and the European experience with Sculptra™ (poly-l-lactic acid). Journal of Drugs in Dermatology, 3(5), 542-547. [42] Goldberg, D., Guana, A., Volk, A., & Daro-Kaftan, E. (2013). Single-arm study for the characterization of human tissue response to injectable poly-L-lactic acid. Dermatologic Surgery, 39(6), 915-922. [43] Lowe, N. J., Maxwell, C. A., & Patnaik, R. (2005). Adverse reactions to dermal fillers: review. Dermatologic Surgery, 31(s4), 1616-1625. [44] Werschler, W. P., et al. (2020). "Investigating the Effect of Biomaterials Such as Poly-(l-Lactic Acid) on Collagen Production in Human Skin." Journal of Cosmetic Dermatology, 19(3), 675-683. [45] Michno et al. (2023). "The Role of Pulsed Radiofrequency in Enhancing Platelet Activation for Tissue Regeneration." *Journal of Pain Research*. [PMC10302511](https://pmc.ncbi.nlm.nih.gov/articles/PMC10302511/). [46] Mishra et al. (2016). "Platelet Rich Plasma: A Short Overview of Certain Bioactive Components." *Bioactive Components in Regenerative Medicine*. [PMC5329835](https://pmc.ncbi.nlm.nih.gov/articles/PMC5329835/). [47] Karpie et al. (2022). "Platelet-Rich Plasma in Plastic Surgery: A Systematic Review." *Therapeutic Advances in Psychopharmacology*. [Karger](https://karger.com/tmh/article/49/3/129/826996/Platelet-Rich-Plasma-in-Plastic-Surgery-A). [48] Lopez-Vidriero et al. (2010). "The Utility of Platelet-Rich Plasma in Modern Orthopedic Practices: A Review of the Literature." *Orthopedic Reviews*. [Scholastica HQ](https://journaloei.scholasticahq.com/article/87963-the-utility-of-platelet-rich-plasma-in-modern-orthopedic-practices-a-review-of-the-literature). [49] Hall et al. (2009). "Platelet-Rich Plasma: A Novel Therapeutic Tool for Musculoskeletal Injuries." *Sports Medicine*. 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![]() 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. ![]() 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. ![]() 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. 7. 3-O-Ethyl Ascorbic Acid (EA) ▌Penetration: Good; water-soluble derivative with enhanced skin penetration compared to L-ascorbic acid (AA) [24][25]. ▌Stability: Highly stable against oxidation due to the ethyl group modification, making it more resistant to degradation than AA [24][26]. ▌Safety and tolerability: Generally well-tolerated, with only rare cases of allergic contact dermatitis reported [25]. ▌Mode of action: Potent antioxidant that converts to vitamin C (AA) in the skin, offering enhanced free radical scavenging and skin brightening properties [24][26]. ▌Effect on collagen: Stimulates collagen synthesis by promoting procollagen I and III gene transcription, similar to AA after conversion [27]. ▌Antioxidative capacity: Excellent; exhibits strong DPPH radical scavenging ability with an IC50 value of 0.032 g/L [26]. ▌Other benefits: Demonstrates skin brightening effects, aids in repairing sun damage, and shows anti-inflammatory properties [24][27]. Pros: Highly stable, easily absorbed by the skin, and offers multiple skin benefits and good tolerability. Cons: May be less potent than pure AA in some aspects, as it requires conversion in the skin. 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. [24] Cosmacon GmbH. "3-O-Ethyl Ascorbic Acid (Vitamin C Derivative)." Cosmacon Glossary, 2025. [25] Iliopoulos F, Sil BC, Moore DJ, Lucas RA, Lane ME. 3-O-ethyl-l-ascorbic acid: Characterisation and investigation of single solvent systems for delivery to the skin. Int J Pharm X. 2019 Jul 19;1:100025. doi: 10.1016/j.ijpx.2019.100025. PMID: 31517290; PMCID: PMC6733298. [26] Liao, W. C., Huang, Y. T., Lu, L. P., & Huang, W. Y. (2018). Antioxidant Ability and Stability Studies of 3-O-Ethyl Ascorbic Acid, a Cosmetic Tyrosinase Inhibitor. Journal of Cosmetic Science, 69(4), 233-243. [27] Boo YC. Ascorbic Acid (Vitamin C) as a Cosmeceutical to Increase Dermal Collagen for Skin Antiaging Purposes: Emerging Combination Therapies. Antioxidants (Basel). 2022 Aug 26;11(9):1663. doi: 10.3390/antiox11091663. PMID: 36139737; PMCID: PMC9495646. ![]() The widespread belief that the epidermis renews itself every 28 days is inaccurate. Epidermal turnover primarily involves keratinocytes, the predominant cell type in the epidermis with 90%. These cells originate in the basal layer (stratum germinativum) and progressively move upward through the epidermal layers, undergoing various changes before being shed from the skin's surface as dead, flaky cells - a process known as desquamation [1]. The keratinocyte journey has several stages:
Epidermal turnover rates vary significantly with age: ▌In young adults: approximately 28-40 days [2] ▌In more mature adults: 60+ days [2] This age-related slowdown is attributed to decreased cell proliferation [3] KERATINOCYTE LIFESPAN The keratinocyte lifecycle can be divided into two main phases: 1. Active life: Approximately 8 to 10 days from mitosis (in the basal layer) to arrival in the stratum corneum [1]. 2. Stratum corneum transit: The period spent in the outermost layer as corneocytes (dead keratinocytes) before shedding [1]. ![]() Epidermal turnover dynamics The total epidermal turnover time, which includes both active life and stratum corneum transit, varies with age: ▌In young adults: The stratum corneum transit time is approximately 20 days [3] ▌In more mature adults: This transit time is lengthened by more than 10 days (approximately 30+ days) [3] This increase in transit time reflects a slowdown in epidermal cell proliferation rather than an increase in cell layers [3] On average, it takes an estimated 40 to 56 days for the keratinocytes in the epidermis to completely turn over [1] Overall epidermal turnover times Total turnover time (including both active life and stratum corneum transit) varies significantly with age. The decline in epidermal cell renewal is not constant throughout adulthood, remaining relatively stable in younger years before dropping more dramatically after age 50 [3]. Several factors influence the epidermal turnover of keratinocytes 1. Age: Epidermal turnover slows with age. In young adults, the process takes approximately 28-40 days, while in older adults it can extend to 60+ days [4]. 2. Growth factors: Epidermal growth factor (EGF) and keratinocyte growth factor (KGF) play crucial roles in regulating keratinocyte proliferation, migration, and differentiation [5]. 3. Transcription factors: p63, particularly the ΔNp63α isoform, is critical for maintaining keratinocyte proliferation and regulating the switch from proliferation to differentiation [4]. 4. Signaling pathways: Notch signaling, IKKα, and IRF6 are involved in regulating keratinocyte differentiation and epidermal turnover [4]. 5. Matrix stiffness: Increased extracellular matrix stiffness promotes keratinocyte proliferation through enhanced EGF signaling [5]. 6. Vitamin D: 1,25-dihydroxyvitamin D3 regulates keratinocyte proliferation and differentiation by modulating calcium concentrations and gene expression [6]. 7. Cell adhesion: Contact with the basal lamina, mediated by integrins, regulates keratinocyte proliferation and differentiation [7]. These factors work in concert to maintain the balance between keratinocyte proliferation in the basal layer and terminal differentiation in the upper layers, ensuring proper epidermal homeostasis and turnover. Improving epidermal turnover can be beneficial for several skin conditions, including:
1. Aging: Enhanced epidermal turnover can help reduce visible signs of aging such as: ▌ Wrinkles and fine lines ▌ Skin sagging ▌ Dull, rough skin texture (the size or the corneocytes is increased - see graph) 2. Acne: Faster skin cell turnover can help prevent acne by: ▌ Reducing the accumulation of dead skin cells that can clog pores ▌ Decreasing the risk of bacteria buildup on the skin surface 3. Hyperpigmentation and age spots: Improved turnover can address patches of darkened skin by promoting the removal of older, pigment-producing cells 4. Dry skin: Enhanced cell turnover can help improve skin hydration and barrier function [8] 5. Sun damage: Accelerated epidermal renewal can aid in repairing and replacing sun-damaged skin cells [9] Several in-office procedures and cosmetic ingredients have been shown to accelerate keratinocyte renewal and epidermal turnover: 1. Hyaluronic acid (HA) production enhancers: ▌1-ethyl-β-N-acetylglucosaminide (β-NAG2) has been shown to increase HA production in the epidermis, leading to accelerated keratinocyte proliferation and differentiation [10]. 2. Retinoids: ▌Topical retinoids, such as tretinoin, can increase epidermal turnover and promote keratinocyte proliferation [11]. 3. Chemical peels: ▌Various chemical peeling agents can stimulate epidermal renewal by inducing controlled damage to the skin [11]. 4. Microdermabrasion: ▌This procedure can promote skin turnover by physically removing the outermost layer of dead skin cells [11] 5. Laser treatments: ▌Certain laser therapies can stimulate epidermal regeneration and increase keratinocyte turnover [11] 6. Liquid Crystal Gel (LCG): ▌A study showed that low concentration LCG can increase epidermal thickness and potentially promote skin turnover [11] Excessive stimulation may lead to adverse effects. Therefore, these treatments should be used under professional guidance and with careful consideration of individual skin conditions. Always consult a qualified healthcare professional to determine what the most suitable approach is for your needs and goals. Take care Anne-Marie References: [1] Iizuka H. Epidermal turnover time. J Dermatol Sci. 1994 Dec;8(3):215-7. doi: 10.1016/0923-1811(94)90057-4. PMID: 7865480. [2] Maeda, K. New Method of Measurement of Epidermal Turnover in Humans. Cosmetics 2017, 4, 47. [3] Grove GL, Kligman AM. Age-associated changes in human epidermal cell renewal. J Gerontol. 1983;38(2):137-42. doi:10.1093/geronj/38.2.137 [4] Koster MI, Roop DR. J Invest Dermatol. 2007;127(11):2432-8. PMID: 17934504. [5] Wickert LE, et al. J Cell Sci. 2018;131(10):jcs215780. PMID: 29661845. [6] Wikipedia contributors. "Keratinocyte." Wikipedia, The Free Encyclopedia. [7] Megías M, et al. "Keratinocyte." Atlas of Plant and Animal Histology. University of Vigo. [8] Farage MA, Miller KW, Elsner P, Maibach HI. Aging Clin Exp Res. 2008;20(3):195-204. doi:10.1007/BF03020230. [9] Yaar M, Gilchrest BA. J Investig Dermatol Symp Proc. 2007;12(1):1-10. doi:10.1038/sj.jidsymp.5650020. [10] Yoshida H, et al. J Dermatol Sci. 2021;101(2):122-131. PMID: 33358097. [11] Musashi M, et al. Cosmetics. 2014;1(3):202-210. doi:10.3390/cosmetics1030202. |
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