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![]() Collagen is a vital component of the skin's extracellular matrix, providing essential structural support and elasticity. Collagen-stimulating treatments, skincare products, and supplements have gained popularity for their effectiveness in gradual prejuvenation and rejuvenation approaches. These methods can help maintain skin health and combat signs of aging when used appropriately. However, it's important to note that excessive collagen stimulation can potentially lead to adverse effects, including fibrosis and skin stiffness, which may be detrimental to overall skin health and beauty. Therefore, a balanced and informed approach to collagen stimulation is crucial for achieving optimal results while minimizing potential risks. TYPES OF COLLAGEN AND THEIR ROLES 1. Type I collagen: Predominantly found in skin, tendons, and bones, providing tensile strength. 2. Type III collagen: Often found alongside Type I, contributing to skin elasticity and firmness. While these types are beneficial for youthful skin, excessive production can lead to fibrotic tissue formation and stiffness [1]. More about collagen types click here EXCESSIVE COLLAGEN STIMULATION Excessive collagen production, particularly type I collagen, can contribute to fibrosis and scarring in pathological conditions: 1. In hypertrophic scars, there is an overproduction of primarily type III collagen, which is later replaced by type I collagen. These scars contain "an overload of primarily type III collagen oriented parallel to the epidermal surface with multiple nodules containing myofibroblasts, large extracellular collagen filaments and abundant acidic mucopolysaccharides" [2]. 2. Many rejuvenating in-office treatments (for example energy based devices)are based on "controlled damage and repair”, thus wound healing. During wound healing, abnormal extracellular matrix (ECM) reconstruction, particularly abnormal collagen remodelling, leads to the formation of hypertrophic scars. In these scars, "thin collagen fibres with increased synthesis and crosslinks result in raised scars" [2]. 3. The relative ratio of type III to type I collagen is reduced in pathological scars compared to unscarred adult dermis. Additionally, hydroxylation of type I collagen was found to be significantly higher in keloids, leading to excessive collagen cross-linking [3]. IN-OFFICE TREATMENTS AND COLLAGEN STIMULATION These treatments aim to maintain or restore natural collagen production rather than overstimulate it to unnatural levels. Some examples are: 1. Exosomes and Polynucleotides: Aim to stimulate healthy collagen production but require careful application. 2. Radiofrequency and Ultrasound: Use heat to remodel collagen. While generally safe, a study by Zelickson et al. [4] reported that excessive heating during RF treatments could potentially lead to collagen denaturation and subsequent fibrosis if not properly controlled. 3. Microneedling: Promotes collagen production but risks scarring if not performed properly. A review by Iriarte et al. [5] noted that while microneedling is generally safe, excessive or improper use could potentially lead to scarring or hyperpigmentation. 4. Laser treatments: Excessive use of ablative lasers can potentially lead to scarring and fibrosis. A study by Hantash et al. [6] found that ablative fractional resurfacing can induce dermal remodeling and new collagen formation, but also noted that improper use could lead to adverse effects. It's important to emphasize that these potential adverse effects are typically associated with improper use, overtreatment, or individual susceptibility rather than being inherent risks of the treatments themselves when performed correctly. More research is needed to fully understand the long-term effects of repeated collagen stimulation treatments on skin structure and function. POTENTIAL RISKS ▌Excessive collagen production: Can lead to fibrosis, characterized by stiff, non-functional tissue: increased extracellular matrix deposition, with collagen being the main component, leading to a drastic reduction of tissue functionality [7]. In skin, this can result in reduced elasticity and increased stiffness. ▌Imbalance in collagen types: Overproduction of certain collagen types can lead to reduced skin elasticity and increased stiffness. The ratio of type I to type III collagen naturally increases with age, which is associated with changes in skin tension, elasticity, and healing [7]. RECOMMENDATIONS FOR SAFE USE ▌ Prejuvenation: Focus on treatments (performed by a professional) that promote balanced collagen production without overstimulation. The effect of a collagen-stimulating procedure is a gradual process and can take up to 12 weeks or longer before a final result. This gradual improvement is due to the time required for the body to produce new collagen in response to the stimulation. Laser treatments, for example, can trigger collagen synthesis deep within the skin, with effects continuing for several months post-treatment [8]. Leave sufficient time in between procedures. Support your skin with a skincare routine tailored to your skintype, goals and use of daily sunscreen. Be very rigorous when it comes to the use of home devices or treatments. Many of them are not well researched or might cause damage when not properly used or performed. ▌Rejuvenation: Opt for treatments or a combination of treatments that complement each other, working in different layers of the skin in different ways. Don't expect a "one-day transformation". Rebuilding collagen takes time and a consistent approach. The skin is not able to replenish what it lost over a period of many years in just a few days [9]. Support in-office collagen stimulating treatments with a good skincare regimen, daily use of sunscreen, healthy lifestyle and diet or supplementation if necessary [10]11]. The effectiveness of combining different treatments for skin rejuvenation has been demonstrated in clinical studies. For instance, a study published in the Journal of Clinical and Aesthetic Dermatology showed that a combination of microneedling and platelet-rich plasma significantly improved skin texture and collagen production compared to microneedling alone [12]. The importance of a consistent skincare regimen and sun protection in maintaining collagen levels has been well-documented. A review in the Archives of Dermatological Research highlighted that daily use of broad-spectrum sunscreen can prevent collagen degradation caused by UV radiation [13]. ![]() While collagen stimulation is beneficial for skin prejuvenation, "banking" or rejuvenation, it is crucial to balance its production to avoid the formation of fibrotic tissue and maintain healthy skin elasticity. Further research is needed to optimize treatment protocols and minimize risks associated with excessive collagen stimulation. Always consult a qualified healthcare professional to determine the most suitable approach for your skin goals, health, and beauty. Take care Anne-Marie References: [1] Wang Kang , Wen Dongsheng , Xu Xuewen , Zhao Rui , Jiang Feipeng , Yuan Shengqin , Zhang Yifan , Gao Ya , Li Qingfeng Extracellular matrix stiffness—The central cue for skin fibrosis Frontiers in Molecular Biosciences 2023 DOI=10.3389/fmolb.2023.1132353 [2] Meirte J, Moortgat P, Anthonissen M, Maertens K, Lafaire C, De Cuyper L, Hubens G, Van Daele U. Short-term effects of vacuum massage on epidermal and dermal thickness and density in burn scars: an experimental study. Burns Trauma. 2016 Jul 8;4:27. doi: 10.1186/s41038-016-0052-x. PMID: 27574695; PMCID: PMC4964043. [3] Zhou Claire Jing , Guo Yuan Mini review on collagens in normal skin and pathological scars: current understanding and future perspective Frontiers in Medicine 2024 [4] Zelickson, B. D., Kist, D., Bernstein, E., Brown, D. B., Ksenzenko, S., Burns, J., ... & Kilmer, S. (2004). Histological and ultrastructural evaluation of the effects of a radiofrequency‐based nonablative dermal remodeling device: a pilot study. Archives of Dermatology, 140(2), 204-209. [5] Iriarte, C., Awosika, O., Rengifo-Pardo, M., & Ehrlich, A. (2017). Review of applications of microneedling in dermatology. Clinical, Cosmetic and Investigational Dermatology, 10, 289-298. [6] Hantash, B. M., Bedi, V. P., Kapadia, B., Rahman, Z., Jiang, K., Tanner, H., ... & Zachary, C. B. (2007). In vivo histological evaluation of a novel ablative fractional resurfacing device. Lasers in Surgery and Medicine, 39(2), 96-107. [7] Wang, C., Rong, Y., Ning, F., & Zhang, G. (2011). The content and ratio of type I and III collagen in skin differ with age and injury. African Journal of Biotechnology, 10(13), 2524-2529. https://doi.org/10.5897/AJB10.1999 [8] Alam, M., Hughart, R., Champlain, A., Geisler, A., Paghdal, K., Whiting, D., Hammel, J. A., Maisel, A., Rapcan, M. J., West, D. P., & Poon, E. (2018). Effect of Platelet-Rich Plasma Injection for Rejuvenation of Photoaged Facial Skin: A Randomized Clinical Trial. JAMA Dermatology, 154(12), 1447-1452. https://doi.org/10.1001/jamadermatol.2018.3977 [9] Ganceviciene, R., Liakou, A. I., Theodoridis, A., Makrantonaki, E., & Zouboulis, C. C. (2012). Skin anti-aging strategies. Dermato-endocrinology, 4(3), 308-319. https://doi.org/10.4161/derm.22804 [10] Katta, R., & Desai, S. P. (2014). Diet and dermatology: the role of dietary intervention in skin disease. The Journal of clinical and aesthetic dermatology, 7(7), 46-51. [11] Addor, F. A. S. (2017). Antioxidants in dermatology. Anais brasileiros de dermatologia, 92, 356-362. https://doi.org/10.1590/abd1806-4841.20175697 [12] Asif, M., Kanodia, S., & Singh, K. (2016). Combined autologous platelet-rich plasma with microneedling verses microneedling with distilled water in the treatment of atrophic acne scars: a concurrent split-face study. Journal of Cosmetic Dermatology, 15(4), 434-443. https://doi.org/10.1111/jocd.12207 [13] Battie, C., & Verschoore, M. (2012). Cutaneous solar ultraviolet exposure and clinical aspects of photodamage. Indian Journal of Dermatology, Venereology, and Leprology, 78, S9-S14. https://doi.org/10.4103/0378-6323.97351
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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. Cold Spring Harbor Perspectives in Biology, 3(1), a004978. https://doi.org/10.1101/cshperspect.a004978 [2] Shuster S, Black MM, McVitie E. "The influence of age and sex on skin thickness, skin collagen and density." British Journal of Dermatology. 1975;93(6):639-643. doi:10.1111/j.1365-2133.1975.tb05113.x. [3] Varani J, Dame MK, Rittie L, Fligiel SE, Kang S, Fisher GJ, Voorhees JJ. Decreased collagen production in chronologically aged skin: roles of age-dependent alteration in fibroblast function and defective mechanical stimulation. Am J Pathol. 2006 Jun;168(6):1861-8. doi: 10.2353/ajpath.2006.051302. PMID: 16723701; PMCID: PMC1606623. [4] Farage MA, Miller KW, Elsner P, Maibach HI. Aging Clin Exp Res. 2008;20(3):195-204. doi:10.1007/BF03020230. [6] Jabłońska-Trypuć, A., Matejczyk, M., & Rosochacki, S. (2016). Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(sup1), 177–183. https://doi.org/10.3109/14756366.2016.1161620 [7] Ledwoń P, Papini AM, Rovero P, Latajka R. Peptides and Peptidomimetics as Inhibitors of Enzymes Involved in Fibrillar Collagen Degradation. Materials (Basel). 2021 Jun 10;14(12):3217. doi: 10.3390/ma14123217. PMID: 34200889; PMCID: PMC8230458. [8] Reilly DM, Lozano J. Skin collagen through the lifestages: importance for skin health and beauty. Plast Aesthet Res. 2021;8:2. http://dx.doi.org/10.20517/2347-9264.2020.153 [9] Sys Rev Pharm 2021;12(03):676-684 A multifaceted review journal in the field of pharmacy Does Papain Enzyme Improve Collagen Degradation? Herman Y. L. Wihastyoko et al. [10] He T, Fisher GJ, Kim AJ, Quan T. Age-related changes in dermal collagen physical properties in human skin. PLoS One. 2023 Dec 8;18(12):e0292791. doi: 10.1371/journal.pone.0292791. PMID: 38064445; PMCID: PMC10707495. Age-related changes in dermal collagen physical properties in ... https://pmc.ncbi.nlm.nih.gov/articles/PMC10707495/ [11]Trujillo, J., & Galligan, J. J. (2024). An overview on glycation: molecular mechanisms, impact on biomolecules, and related diseases. Glycoconjugate Journal. https://doi.org/10.1007/s10719-024-10254-y [12]Sadowska-Bartosz, I., & Bartosz, G. (2022). Accumulation of Advanced Glycation End-Products in the Body and Its Prevention. Nutrients, 14(19), 4072. https://doi.org/10.3390/nu14194072 [13] Sadowska-Bartosz, I., & Bartosz, G. (2015). Prevention of protein glycation by natural compounds. Molecules, 20(2), 3309-3334. [14] Uribarri, J., et al. (2015). Dietary advanced glycation end products and their role in health and disease. Advances in Nutrition, 6(4), 461-473. [15] Guilbaud, A., et al. (2016). How can diet affect the accumulation of advanced glycation end-products in the human body? Foods, 5(4), 84. [16] Wu, M., Cronin, K., & Crane, J. (2023). Biochemistry, Collagen Synthesis. In StatPearls [Internet]. StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507709/ [17] Edgar, S., Hopley, B., Genovese, L. et al. Effects of collagen-derived bioactive peptides and natural antioxidant compounds on proliferation and matrix protein synthesis by cultured normal human dermal fibroblasts. Sci Rep 8, 10474 (2018). https://doi.org/10.1038/s41598-018-28492-w [18] Frontiers | Collagen peptides affect collagen synthesis and the expression of collagen, elastin, and versican genes in cultured human dermal fibroblasts https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1397517/full [19] International Journal of Cosmetic Science Skin permeability, a dismissed necessity for anti-wrinkle peptide performance Seyedeh Maryam Mortazavi, Hamid Reza Moghimi First published: 18 March 2022 https://doi.org/10.1111/ics.12770 [20] Pickart L, et al. 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*. [Reumatologia Clinica](https://www.reumatologiaclinica.org/en-platelet-rich-plasma-a-new-articulo-S2173574312001554). ![]() The UV Index (UVI) is a valuable tool for assessing the strength of ultraviolet (UV) radiation from the sun at any given location and time. The UVI values are determined using the STAR (System for Transfer of Atmospheric Radiation) model. This model takes into account various atmospheric conditions to estimate UV radiation levels. The values provided reflect typical conditions for each location and serve as reference points. Actual UV Index readings can vary due to local factors, such as temporary changes in ozone levels and other atmospheric conditions. The values range from 0 to 11+, serving as a standardized guide for sun protection measures. This helps us understand the potential for skin damage based on UV exposure levels. They are specified for the 21st of each month across different regions. Higher UVI values indicate a greater risk of harm, particularly concerning sunburn, DNA damage, premature skin aging and hyperpigmentation [1][2]. HIGHEST AND LOWEST UV INDEX VALUES Highest UV Index The highest recorded UV Index values can reach 12 or more, especially in regions near the equator, high-altitude areas, and places with low ozone levels. The Atacama Desert in Chile has documented peaks as high as 20, highlighting the extreme UV exposure possible in certain environments [2]. Lowest UV Index The lowest values are typically observed at night or during winter months in polar regions, where solar angles are significantly reduced, often resulting in readings close to zero [2][3]. GEOGRAPHIC INFLUENCES ON UV LEVELS UV exposure varies widely across different geographical regions and withing the regions: ▌Europe: Generally experiences moderate UV levels due to higher latitudes and frequent cloud cover [4]. ▌Asia: Significant variability; tropical areas encounter high UV levels while northern regions have lower indices [2]. ▌Australia: Known for high UV exposure, particularly during summer months, due to its proximity to the equator and clearer skies. ▌USA: Southern states typically report higher UV indices compared to their northern counterparts. ▌Latin America: High UV indices are prevalent near the equator, while southern regions like Argentina experience lower values [2][3]. ▌Altitude: Higher altitudes receive more intense UV radiation due to a thinner atmosphere [2]. ▌Reflection: Beaches can experience increased UV levels due to sunlight reflecting off water and sand [3]. ▌Northern vs. Southern hemisphere: The Southern hemisphere generally has higher UV levels attributed to less atmospheric pollution and ozone depletion [2]. ▌Equatorial regions: These areas maintain consistently high UV indices throughout the year due to direct sunlight [2][3]. ![]() INDOOR vs OUTDOOR UV EXPOSURE The UV Index indoors is significantly lower than outdoor levels on a sunny day. This is primarily due to the filtering effect of window glass, which blocks most UVB radiation. On a clear day, outdoor UV levels can reach up to 8,000 µW/cm², while indoor levels near a window may be as low as 250 µW/cm², dropping further with distance from the window. The indoor UVI reduction is primarily due to the filtering effect of glass windows, which block most UVB (320–400 nm) radiation while allowing some UVA (320–400 nm) rays to penetrate and can still contribute to premature skin aging, hyperpigmentation and DNA damage. Blue Light (400–495 nm): Part of visible light spectrum; penetrates glass easily. High energy Visible Light is responsible for 50% of the free radical activity [5] and like UV radiations contributes to premature skin aging, hyperpigmentation and DNA damage. Factors influencing indoor UV exposure include window size, orientation, and surrounding obstructions like trees. Direct and indirect exposure ▌Direct exposure occurs when sunlight directly enters through windows. ▌Indirect (Diffuse) exposure results from sunlight scattering off surfaces or atmospheric particles. While diffuse exposure is reduced by walls and roofs, it can still penetrate through windows [3]. Factors affecting indoor exposure 1. Window glass: Standard glass blocks most UVB but allows some UVA and High energy Visible Light through. 2. Sky view: More visible sky from indoors increases diffuse UV exposure. 3. Distance from windows: The intensity of UV radiation decreases with distance from windows due to the inverse square law [3]. 4. Window orientation and size: Larger windows facing south (in the Northern Hemisphere) or north (in the Southern Hemisphere) allow more sunlight into indoor spaces [3]. 5. Scattering (indirect – diffuse exposure) ![]() CHANGING UVI OVER TIME There is scientific evidence indicating that the UV Index (UVI) is influenced by various environmental factors, including changes in ozone levels and climate conditions, which can affect UV radiation exposure over time. 1. UV radiation: A study by Fountoulakis et al. (2020) analyzed long-term changes in UV-B radiation and found that variations in UV levels are primarily driven by changes in aerosols and total ozone, with significant regional differences observed. The study indicates that while some areas have experienced increases in UV-B irradiance, others have shown decreases, particularly during summer months in polar regions due to improvements in ozone levels [6]. 2. Impact of ozone depletion: Research has shown that the decline of stratospheric ozone has historically led to increased UV radiation at certain wavelengths. For instance, a study by Bais et al. (2011) projected that UV irradiance would likely return to its 1980 levels by the early 21st century at northern mid-latitudes and high latitudes, suggesting ozone recovery influences UV radiation levels [7].While standard windows block most harmful UVB rays, damaging UVA and blue light (or HEVIS) can still penetrate indoors, affecting skin´s beauty and health. Awareness of these factors and UV Index enables you to take appropriate protective measures against harmful effects of sunlight even indoors while considering the benefits of controlled exposure for vitamin D synthesis [3]. Take care Anne-Marie References [1] Federal Office for Radiation Protection (BfS). (n.d.). What is the UV Index? Retrieved December 7, 2024, from bfs.de/EN/topics/opt/uv/index/introduction/introduction_node.html [2] Fioletov V, Kerr JB, Fergusson A. The UV index: definition, distribution, and factors affecting it. Can J Public Health. 2010;101(4):I5-9. doi: 10.1007/BF03405303. [3] Heckman CJ, Liang K, Riley M. Awareness and impact of the UV index: A systematic review of international research. Prev Med. 2019;123:71-83. doi: 10.1016/j.ypmed.2019.03.004. [4] World Health Organization. (n.d.). Radiation: The UV index. Retrieved December 7, 2024, from who.int/news-room/questions-and-answers/item/radiation-the-ultraviolet-(uv)-index [5] Albrecht S et al. Effects on detection of radical formation in skin due to solar irradiation measured by EPR spectroscopy. Methods. 2016;109:44-54. [6] Fountoulakis I et al. Long-term changes in UV-B radiation. Atmos Chem Phys. 2020;20(5):3075-3091. [7] Bais AF et al. Projections of UV radiation changes in the 21st century: impact of ozone recovery and cloud effects. Atmos Chem Phys. 2011;11(20):7533-7545. doi: 10.5194/acp-11-7533-2011 [8] Eleftheratos K et al. Ozone, DNA-active UV radiation, and cloud changes due to enhanced greenhouse gas concentrations. Atmos Chem Phys. 2022;22:12827–12855. doi: 10.5194/acp-22-12827-2022 12/7/2024 Comments The dark side of vitamin C![]() Although Vitamin C in topical applications has many benefits, it also has a dark side; it can be harmful in its oxidised form, temporarily darken the skin and become a pro-oxidant. When vitamin C (ascorbic acid) is exposed to air, light, or heat, it undergoes chemical changes similar to how sugar turns brown when heated. This process doesn't need any special helpers (like enzymes); it just happens because of the conditions around it. Over time, vitamin C breaks down and forms new compounds that have a brown color, much like how sugar becomes caramel. This process is called non-enzymatic oxidation. Oxidized vitamin C can have both beneficial and potentially harmful effects on the skin. 1. ANTIOXIDANT Vitamin C is primarily known for its antioxidant properties, effectively neutralizing reactive oxygen species (ROS) and reducing oxidative stress in the skin. This helps prevent DNA damage and collagen degradation, contributing to anti-aging benefits and improved skin health and beauty [1][2][3]. How vitamin C acts as an antioxidant and undergoes oxidation in your skin Imagine vitamin C as a brave knight patrolling your skin, constantly on guard against harmful invaders called free radicals. These free radicals can damage skin cells, much like how rust can damage metal. Vitamin C, in its role as an antioxidant, sacrifices part of itself (donating an electron) to neutralize these free radicals, preventing them from causing harm. ▌ InInitial defense: When vitamin C donates an electron, it transforms into a less powerful form called the ascorbate radical, similar to a knight losing a piece of armor but still able to fight. ▌ Continued protection: If more free radicals attack, vitamin C can further degrade into dehydroascorbic acid. This form can be regenerated with the help of other antioxidants like glutathione, similar to allies helping the knight repair its armor. ▌ Synergistic effects: Using vitamin C with other antioxidants in skincare products enhances its protective abilities, much like having a team of knights working together for stronger defense. I prefer combining Vitamin C with Licochalcone A for comprehensive skin protection. Vitamin C acts quickly in the skin's outer layer, providing immediate extracellular defense. Meanwhile, Licochalcone A offers long-lasting, intracellular protection against free radicals induced by both UV and High Energy Visible Light, which penetrate deeper into the skin. This synergistic approach ensures a more complete and sustained antioxidant effect. ▌ Final sacrifice: Without support, vitamin C eventually breaks down into other compounds and loses its protective power completely. 2. PRO-OXIDANT At high concentrations, vitamin C can exhibit pro-oxidative properties, generating hydrogen peroxide (H2O2) and leading to increased oxidative stress, particularly when vitamin C interacts with transition metals (Cu and Fe), which can catalyze the formation of harmful radicals [4][5]. This increases the risk of irritation or damage to skin cells. Copper (Cu): Copper compounds can penetrate the skin and participate in redox reactions [6]. Copper can catalyze the oxidation of ascorbate and participate in the Haber-Weiss reaction, generating free radicals [7]. Iron (Fe): Iron can participate in the metal-catalyzed Haber-Weiss reaction, also known as the superoxide-driven Fenton reaction, which produces harmful free radicals [7]. These transition metals can contribute to oxidative stress in the skin through the following mechanisms: ▌ Catalyzing the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) [8]. ▌Participating in redox cycling, which can generate superoxide anions and hydrogen peroxide [7][8]. ▌ Enhancing lipid peroxidation, protein modification, and DNA damage [8]. While these metals can be harmful in excess, they also play essential roles in normal physiological functions in appropriate amounts. 3. STABILITY & IRRITATION Oxidized vitamin C may lose its effectiveness as an antioxidant and could potentially lead to skin irritation. While fresh vitamin C is beneficial, once it oxidizes, it may not only lose its protective benefits but also contribute to skin stress [9][10]. 4. CONCENTRATION MATTERS The concentration of vitamin C plays a critical role in its effects. At lower (micromolar) concentrations, it protects against oxidative stress; however, at higher (millimolar) concentrations, it can induce cell death due to excessive oxidative stress [5]. Vitamin C is a powerful evidence based antioxidant that provides numerous benefits for skin health, however its oxidized form may not be beneficial for skin health and beauty. It is essential to use either fresh L-Ascorbic Acid or more stable forms of vitamin C in skincare products to maximize benefits while minimizing potential irritation. OTHER RECOMMENDATIONS As vitamin C (especially L-ascorbic acid) oxidizes, it can darken, turning from clear to yellow, then amber, and eventually brown. ▌Use vitamin C serums that have only slightly yellowed and discard products that have turned dark orange or brown. Be aware of signs of oxidation, such as changes in color or smell. ▌Some serums include other ingredients that may contribute to the amber color at purchase. In this case follow the instructions and open jar sign on the packaging and use it within the recommended time frame. ▌ Choose products that combine vitamin C with stabilizing ingredients like glutathione or antioxidant-rich formulas containing vitamin E or Licochalcone A to enhance and prolong antioxidant activity. ▌Store your vitamin C serum properly (cool, dark place. Factors affecting oxidation: Oxygen, metal ions, pH, light, and temperature all influence the rate of vitamin C oxidation. ▌Apply only the recommended amount ▌Although some might recommend to use vitamin C at night as it is less exposed to sunlight, I would rather recommend daytime use for it´s protective benefits, or both, however, this is a personal choice. Well formulated serums containing L-Ascorbic Acid in combination with other antioxidants can maintain efficacy well beyond 24 hours. Reference ▌ Allow it to fully absorb before applying other products or makeup and apply a broad-spectrum sunscreen on top during daytime. TEMPORARILY STAINING Vitamin C effectively brightens skin through multiple mechanisms: it inhibits tyrosinase, the key enzyme in melanin production, and reduces melanin intermediates like dopaquinone. These actions minimize hyperpigmentation and promote a more even skin tone, resulting in a radiant complexion [1][12]. However, vitamin C can also darken the skin temporarily. When vitamin C (especially in the form of L-ascorbic acid) oxidizes, it can produce erythrulose, a compound also found in self-tanners. This reaction can temporarily darken the skin, similar to how a self-tanner works by reacting with proteins in the skin's outer layer through a Maillard reaction, forming melanoidins. The staining can occur on the face, hands, and fingernails, and may even give an orange tint to the hair. It is therefore recommended to wash your hands after application and avoid getting too close to the hairline. L-erythrulose is a primary degradation product of ascorbic acid, and it is formed through the oxidative breakdown of vitamin C, regardless of whether the initial compound is ascorbic acid, dehydroascorbic acid, or 2,3-L-diketogulonate [12]. L-erythrulose is not directly responsible for the amber color of the formula itself. Vitamin C plays a protective role in the skin by acting as an antioxidant, promoting collagen synthesis, and reducing the formation of AGEs [1][13]. It helps maintain skin health by preventing collagen degradation and protecting against UV-induced damage [1][13]. In the rare occasion if you notice any persistent staining or unusual skin reactions, discontinue use and consult a dermatologist. Take care Anne-Marie References [1] Al-Niaimi F, Chiang NYZ. J Clin Aesthet Dermatol. 2017 Jul;10(7):14-17. [2] Khalid A, et al. J Health Rehabil Res. 2024;4(2):1489-1494. [3] Pullar JM, et al. Nutrients. 2017 Aug 12;9(8):866. [4] Kaźmierczak-Barańska J, et al. Nutrients. 2020 May 21;12(5):1501. [5] Chakraborty A, Jana NR. ACS Appl Mater Interfaces. 2017 Dec [6] Hostynek JJ, Maibach HI. Toxicol Mech Methods. 2006;16(5):245-65. [7] Buettner GR, Jurkiewicz BA. Radiat Res. 1996 May;145(5):532-41. [8] Chaudhary P, et al. Front Chem. 2023 May 10;11:1158198. 6;9(48):41807-41817. [9] Jelodar G, et al. Zahedan J Res Med Sci. 2023;25(4):e4037. [10] Podmore ID, et al. Nature. 1998 Apr 9;392(6676):559. [11] De Dormael R, et al. Vitamin C Prevents UV Pigmentation: Meta-analysis. J Clin Aesthet Dermatol. 2019;12(2):E53-E59. [12] Simpson GL, Ortwerth BJ. Biochim Biophys Acta. 2000;1501(1):12-24. [13] Wang K, et al. Role of Vitamin C in Skin Diseases. Front Physiol. 2018;9:819. 12/7/2024 Comments Regenerative aesthetics: Wound healing & growth factors for collagen biostimulation![]() Interestingly, the biochemical pathways involved in skin rejuvenation and wound healing share notable similarities. This connection forms the basis for many clinical regenerative aesthetical treatments designed to stimulate collagen production. Interventions, such as chemical peelings and energy-based devices, work by creating controlled damage (wound) to trigger the skin's natural healing response, while topical treatments can include growth factors to boost collagen synthesis (biostimulation) and promote skin regeneration [1]. Wound healing is a complex biological process that relies on the synchronized actions of various cell types, guided by growth factors and cytokines [2]. Central to this regenerative process is collagen, a crucial component of the extracellular matrix (ECM) giving skin strenght and structure, however is declining as we age and therefore a primary target for skin (pre)rejuvenation treatments. Collagen's plays vital roles throughout the wound healing process [3]. The wound healing process has four distinct however overlapping phases (illustration): [3][4] 1. Hemostasis: ▌Platelets release growth factors including PDGF, IGF, TGF-α/β, and EGF, initiating the wound healing cascade and attracting immune cells to the wound site [3][5]. 2. Inflammation: ▌ Growth factors and cytokines released by platelets and immune cells promote inflammation and cellular migration [5]. ▌Macrophages produce additional growth factors, including FGF, which induces fibroblast activation and proliferation [5]. 3. Proliferation: ▌PDGF and TGF-β stimulate fibroblast migration, proliferation, and collagen production [4][5]. ▌FGF promotes fibroblast proliferation and angiogenesis [4]. ▌VEGF is crucial for angiogenesis and the formation of granulation tissue [5][6]. ▌KGF and EGF facilitate reepithelialization by stimulating keratinocyte migration and proliferation [6]. 4. Remodeling: ▌ TGF-β influences the transition from type III to type I collagen, improving wound strength [3][5]. ▌This phase can last from 3 weeks to 2 years post-injury [5]. This explains why biostimulation of collagen production is a gradual process and ultimate results can take weeks or even months. Initially, type III collagen is deposited in the granulation tissue, forming a loose matrix with other components like hyaluronic acid and fibronectin [3][5]. ▌During remodeling, type III collagen is gradually replaced by stronger type I collagen, increasing the mechanical strength of the tissue [3][5]. ▌The collagen fibers are rearranged into a more organized lattice structure, although newly formed scar tissue has only 70-80% of the tensile strength of intact skin [5]. ▌ Fibroblasts and myofibroblasts, stimulated by growth factors, are responsible for collagen production and remodeling [5][7]. Impairments in any phase of wound healing can lead to chronic, non-healing wounds, which is a growing concern in healthcare [3]. ![]() GROWTH FACTORS Growth factors (GF) are naturally occurring polypeptides secreted by various cells including the dermal fibroblast, facilitating signaling pathways between and within cells throughout the healing phases [6]. These factors, including Platelet-Derived Growth Factor (PDGF), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), Transforming Growth Factor-β (TGF-β), among others, function synergistically to guide the wound from injury to complete tissue regeneration [4]. Topical applied growth factors can support this skin rejuvenation healing process [8][9]. However, direct application of growth factors to wounds faces challenges such as rapid degradation in the wound environment and the need for high doses to achieve clinical efficacy [4]. COLLAGEN Collagen, whether in its natural fibrillar form or as soluble parts in the wound environment, closely interacts with these growth factors [3]. Collagen not only provides structural support to the skin, it also actively participates in cell signaling, influencing key processes such as hemostasis, inflammation resolution, angiogenesis, and matrix remodeling [3][10]. The interaction between growth factors and collagen creates a lively environment that is essential for effective wound healing. Some studies suggest potential benefits of oral collagen supplements [11][12][13] and topical collagen products [14] for wound healing. A high quality collagen powder does have right building blocks (amino acids: proline, glycine and hydroxyproline) for collagen production. The effects may vary depending on the type of wound, collagen formulation, and application method. Exosomes [15] Exosomes isolated from stem cell cultures contain various growth factors, including EGF, VEGF, TGF, HGF, FGF, IGF, and PDGF. These growth factors play crucial roles in skin regeneration, anti-aging effects, and wound healing by promoting fibroblast proliferation and collagen synthesis. The use of skin´s own healing power via a regenerative aesthetic treatment causing controlled injury is collagen biostimulatory and the use of topical growth factors, exosomes and oral collagen powders may enhance the outcome. 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] Goldman R. Growth factors and chronic wound healing: past, present, and future. Adv Skin Wound Care. 2004 Jan-Feb;17(1):24-35. doi: 10.1097/00129334-200401000-00012. PMID: 14752324. [2] Barrientos S, Brem H, Stojadinovic O, Tomic-Canic M. Clinical application of growth factors and cytokines in wound healing. Wound Repair Regen. 2014 Sep-Oct;22(5):569-78. doi: 10.1111/wrr.12205. PMID: 24942811; PMCID: PMC4812574. [3] Mathew-Steiner SS, Roy S, Sen CK. Collagen in Wound Healing. Bioengineering (Basel). 2021 May 11;8(5):63. doi: 10.3390/bioengineering8050063. PMID: 34064689; PMCID: PMC8151502. [4] Vaidyanathan, L. (2021). Growth Factors in Wound Healing – A Review. Biomedical and Pharmacology Journal, 14(3). DOI: https://dx.doi.org/10.13005/bpj/2249 [5] Park JW, Hwang SR, Yoon IS. Advanced Growth Factor Delivery Systems in Wound Management and Skin Regeneration. Molecules. 2017 Jul 27;22(8):1259. doi: 10.3390/molecules22081259. PMID: 28749427; PMCID: PMC6152378. [6] Barrientos, S., Stojadinovic, O., Golinko, M.S., Brem, H., & Tomic-Canic, M. (2008). Growth factors and cytokines in wound healing. Wound Repair and Regeneration, 16(5), 585–601. [7] Hochstein, A. O., & Bhatia, A. (2014). Collagen: Its Role in Wound Healing. Podiatry Management, 33(6), 103-110. [8] Zarei, F., & Soleimaninejad, M. (2018). Role of growth factors and biomaterials in wound healing. Artificial Cells, Nanomedicine, and Biotechnology, 46(sup1), 906–911. [9] La Monica, F.; Campora, S.; Ghersi, G. Collagen-Based Scaffolds for Chronic Skin Wound Treatment. Gels 2024, 10, 137. https://doi.org/10.3390/gels10020137 [10] Shi, S., Wang, L., Song, C. et al. Recent progresses of collagen dressings for chronic skin wound healing. Collagen & Leather 5, 31 (2023). https://doi.org/10.1186/s42825-023-00136-4 [11] Bagheri Miyab K, Alipoor E, Vaghardoost R, Saberi Isfeedvajani M, Yaseri M, Djafarian K, Hosseinzadeh-Attar MJ. The effect of a hydrolyzed collagen-based supplement on wound healing in patients with burn: A randomized double-blind pilot clinical trial. Burns. 2020 Feb;46(1):156-163. doi: 10.1016/j.burns.2019.02.015. Epub 2019 Dec 16. PMID: 31859087. [12] Choi FD, Sung CT, Juhasz ML, Mesinkovsk NA. Oral Collagen Supplementation: A Systematic Review of Dermatological Applications. J Drugs Dermatol. 2019 Jan 1;18(1):9-16. PMID: 30681787. [13] Katayoun Bagheri Miyab, Elham Alipoor, Reza Vaghardoost, Mohsen Saberi Isfeedvajani, Mehdi Yaseri, Kurosh Djafarian, Mohammad Javad Hosseinzadeh-Attar, The effect of a hydrolyzed collagen-based supplement on wound healing in patients with burn: A randomized double-blind pilot clinical trial, Burns, Volume 46, Issue 1, 2020, Pages 156-163,ISSN 0305-4179, https://doi.org/10.1016/j.burns.2019.02.015. [14] Friedman, A., et al. (2019). A Head-to-Head Comparison of Topical Collagen Powder to Primary Closure for Acute Full-Thickness Punch Biopsy-Induced Human Wounds: An Internally Controlled Pilot Study. Journal of Drugs in Dermatology. [15] Kim, J. Y., & Park, Y. H. (2017). Stem cell-derived exosome containing high amount of growth factors (World Intellectual Property Organization Patent No. WO2017123022A1). Google Patents. ![]() 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. ![]() Peptides have emerged as a powerhouse skincare ingredient, captivating both consumers and aesthetic healthcare professionals. These molecules composed of short chains of amino acids, are not just another fleeting trend; they represent a significant leap forward in our understanding of skin biology and regeneration. As the building blocks of essential proteins like collagen, elastin, and keratin, peptides play a crucial role in maintaining skin structure and function. Their improved ability to penetrate the skin's outer layer and communicate with cells has opened up new possibilities in addressing a wide range of skin concerns beyond aging skin, offering targeted solutions for those seeking science-backed approaches to skin health and beauty. WHAT ARE PEPTIDES? Peptides are short chains of amino acids, typically consisting of 2-50 amino acids, linked by peptide bonds. [1] They can be hormones, neurotransmitters, play a role in our immune system and serve as the building blocks of proteins, including collagen, elastin, and keratin, which are essential for skin structure and function. [2] BODY´S OWN PEPTIDES The exact number of peptides in the brain, body, and skin is not precisely defined due to the complexity and diversity of peptide structures and functions. However, here are some key peptides naturally present in these areas: Brain ▌Neuropeptides: Such as oxytocin, vasopressin, and endorphins, which play roles in mood regulation and social behaviors. ▌Enkephalins: Involved in pain modulation. Body ▌Insulin: Regulates glucose metabolism. ▌Glucagon: Works with insulin to maintain blood sugar levels. ▌Growth hormone: Stimulates growth and cell reproduction. Sometimes off label prescribed in regenerative medicine. Skin ▌Collagen peptides: Provide structural support and elasticity. ▌Elastin peptides: Contribute to skin's elasticity and resilience. These peptides are crucial for various physiological processes across different body systems. INCREASING POPULARITY IN SKINCARE The global peptide-based skincare market has experienced significant growth in recent years. ▌ The global peptide-based cosmetics market is projected to reach $39.9 billion by 2028, with a compound annual growth rate (CAGR) of 6.2% from 2021 to 2028. ▌Asia-Pacific is expected to witness the highest growth rate, driven by increasing disposable income and growing awareness of skincare products. ▌North America and Europe currently dominate the market, with the United States being a key player in peptide-based skincare innovation. ![]() MECHANISMS OF ACTION Peptides in skincare products primarily function through three main mechanisms: 1. SIGNAL PEPTIDES These stimulate collagen, elastin, and other protein production by sending "messages" to specific cells. [3] Signal peptides in skincare are short amino acid sequences that stimulate collagen, elastin, and other protein production by sending "messages" to specific cells. Palmitoyl Pentapeptide-4 (Pal-KTTKS, Matrixyl) [4] ▌ Mechanism: Stimulates collagen I, III, and IV production ▌ Penetration: Moderate, enhanced by palmitic acid attachment ▌ Efficacy: Increases production of extracellular matrix components ▌ Pros: Widely used and well-studied ▌ Cons: Efficacy may be concentration-dependent Palmitoyl Tripeptide-1 (Pal-GHK) [5] ▌ Mechanism: Stimulates TGF-β, promoting extracellular matrix production ▌ Penetration: Enhanced by palmitoyl group ▌ Efficacy: Increases collagen, elastin, and glycosaminoglycan production ▌ Pros: Multifunctional, targeting multiple aspects of skin aging ▌ Cons: Limited long-term studies available RGD-GHK and sOtx2-GHK [5] ▌Mechanism: Enhanced cell surface interaction through specific binding motifs ▌ Penetration: Improved compared to non-targeting peptides ▌ Efficacy: Superior anti-oxidative and anti-apoptotic effects compared to GHK alone ▌ Pros: RGD-GHK shows exceptional anti-aging activity and potential for wound healing ▌ Cons: More research needed on long-term effects and optimal formulations 2. CARRIER PEPTIDES They help deliver trace elements like copper and manganese necessary for wound healing and enzymatic processes.[3] GHK-Cu (Copper Tripeptide-1) [4] ▌ Mechanism: Delivers copper to cells, promoting wound healing and collagen synthesis ▌ Penetration: Moderate, enhanced by copper chelation ▌ Efficacy: Promotes wound healing and has antioxidant properties ▌ Pros: Well-studied for wound healing applications ▌ Cons: Potential for oxidative damage if used in high concentrations 3. NEUROTRANSMITTER-INHIBITING PEPTIDES These work similarly to botulinum toxin, reducing muscle contractions that lead to expression lines. [3] Acetyl Hexapeptide-3 (Argireline) [4] ▌ Mechanism: Inhibits SNARE complex formation, reducing muscle contractions ▌ Penetration: Limited due to larger size ▌ Efficacy: Reduces appearance of expression lines ▌ Pros: Non-invasive alternative to botulinum toxin ▌ Cons: Effects are temporary and may vary between individuals I would not want to compare the efficacy to botulinum toxin The challenge with peptides in skincare is their skin permeability. Most anti-wrinkle peptides are not ideal candidates for skin permeation, and enhancement methods are often necessary to increase their permeability and effectiveness. [5] Researchers are exploring ways to improve peptide delivery and efficacy, such as designing novel targeting peptide motifs to enhance the interaction between cosmetic peptides and the cell surface. [5] SOME OTHER PEPTIDES USED IN SKINCARE 4. Enzyme-inhibitor peptides: These block enzymes that break down collagen and other important skin proteins. 5. Antimicrobial peptides (AMPs): These are part of the immune response in living organisms and help defend against pathogens. 6. Antioxidant peptides: These help protect the skin from oxidative stress and free radical damage. BENEFITS OF PEPTIDES IN SKINCARE 1. Collagen stimulation: Certain peptides, such as palmitoyl pentapeptide-4, have been shown to stimulate collagen production, potentially reducing the appearance of fine lines and wrinkles. [6] 2. Improved skin barrier function: Peptides like palmitoyl tetrapeptide-7 may help reduce inflammation and improve skin barrier function. [7] 3. Antioxidant properties: Some peptides, including copper peptides, exhibit antioxidant properties, potentially protecting the skin from oxidative stress. [8] 4. Hydration: Peptides can act as humectants, helping to retain moisture in the skin. [9] 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..[1][2] 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. [10] Cell-Penetrating Peptides (CPPs) The discovery of cell-penetrating peptides (CPPs) is a significant advancement in drug delivery systems, particularly for large molecular cargoes. [11][12] Key features of CPPs include: 1. Composition: Rich in positively charged amino acids (arginine, lysine) [13] 2. Function: Ability to cross cell membranes [14] 3. Cargo capacity: Can transport large molecules into cells [15] 4. Potential applications: Delivery of therapeutic agents, including nucleic acids [12][15] 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. [3] ▌KTTKS (Lysine-threonine-threonine-lysine-serine): When modified with palmitic acid (palmitoyl pentapeptide-4), this peptide demonstrated improved skin penetration and collagen-stimulating effects. [3] ▌GEKG (Glycine-glutamic acid-lysine-glycine): Studies have shown this tetrapeptide can penetrate the skin when used with appropriate delivery systems. [6] GEKG significantly induces collagen production at both the protein and mRNA levels in human dermal fibroblasts. [7] 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 [7] boosts collagen, hyaluronic acid, and fibronectin production by dermal fibroblasts. [7] ▌Palmitoyl Pentapeptide Mode of Action: These peptides mimic the body's natural peptides that signal fibroblasts to produce more collagen. [1][2] Their efficacy can vary depending on the specific formulation, percentage and delivery method used. EVEN MORE PEPTIDES 1. Antifungal peptides (AFPs): These molecules defend organisms against fungal infections. 2. Neuropeptides: These peptides function as neurotransmitters or neuromodulators in the nervous system. 3. Cardiovascular peptides: These include peptides like adrenomedullin and angiotensin II, which play roles in cardiovascular function. 4. Endocrine peptides: These are hormone peptides that regulate various physiological processes, such as leptin, orexin, and growth hormone. 5. Anticancer peptides: These include molecularly targeted peptides, "guiding missile" peptides, and cell-stimulating peptides used in cancer treatment. 6. Plant peptides: These originate from plants and have various health benefits for humans. They can be incoroprated in skincare formulations. 8. Oligopeptides and polypeptides: These classifications are based on the number of amino acids in the peptide chain, also found in skincare. 9. Ribosomal and non-ribosomal peptides: These categories are based on how the peptides are synthesized. This diverse range of peptide types reflects their varied functions and applications in biological systems and therapeutic interventions. 10. Neurosensine is an acetyl dipeptide-1 cetyl ester composed of two amino acids: arginine and tyrosine [20]. Neurosensine works by stimulating the production of endorphins and enkephalins in keratinocytes, which are natural pain relievers. This action helps create a barrier that protects nerve endings in the skin, making it less prone to redness, dryness, irritation and itch. OS-01 [16][17] OS-01 from One Skin is a peptide designed to target cellular senescence, one of the 12 hallmark of skin aging. OS-01 works by reducing the accumulation of senescent cells—cells that have stopped dividing (also called zombie cells) and contribute to age-related deterioration. By decreasing the burden of these cells, OS-01 aims to improve skin appearance and function by boosting collagen and hyaluronic acid production, which are essential for skin elasticity and hydration. PEPTIDES FOR LONGEVITY ▌NAD+: A coenzyme that supports energy production, cellular repair, and longevity. It plays a role in DNA repair and declines with age. [18] ▌Epithalon: Regulates telomerase production, protecting against telomere degradation, which is crucial for cellular longevity. Research conducted by Khavinson et al. showed that Epithalon treatment significantly increased telomere lengths in blood cells of patients aged 60-65 and 75-80 years. ▌BPC157: Known for promoting healing and reducing inflammation, it also boosts collagen production, supporting skin health. [19] COLLAGEN PEPTIDE POWDERS. Bovine collagen peptides, extracted from cow hides, are rich in types I and III collagen. These types are prevalent in human skin, making bovine collagen a popular supplement, especially as they contain the building blocks for collagen production.. Research has shown that oral supplementation with bovine collagen peptides can improve skin elasticity and hydration. Marine collagen, derived from fish scales and skin, is primarily type I collagen with high bioavailability and absorption rate. Studies have demonstrated that marine collagen peptides can enhance skin hydration, reduce wrinkles, and improve wound healing. Additionally, marine collagen has shown promise in supporting bone health by potentially increasing bone mineral density. Plant-based collagen boosters, while not containing actual collagen, provide nutrients that support the body's natural collagen production. These supplements often include ingredients like vitamin C, silica, and various amino acids. Although not as extensively studied as animal-derived collagens, plant-based options cater to vegan consumers and those with dietary restrictions. In powder form they can easily be mixed into beverages or foods. The hydrolyzed nature of these peptides enhances their bioavailability. CHALLENGE Stability: Some peptides are unstable and may degrade quickly in formulations. Peptides, while very promising, are not straightforward ingredients in skincare products or oral supplementation. Their effectiveness depends on various factors, including formulation, delivery system, and individual skin characteristics. 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] Edgar, S., Hopley, B., Genovese, L. et al. Effects of collagen-derived bioactive peptides and natural antioxidant compounds on proliferation and matrix protein synthesis by cultured normal human dermal fibroblasts. Sci Rep 8, 10474 (2018). https://doi.org/10.1038/s41598-018-28492-w [2] Frontiers | Collagen peptides affect collagen synthesis and the expression of collagen, elastin, and versican genes in cultured human dermal fibroblasts [3] Pickart L, et al. GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. Biomed Res Int. 2015;2015:648108. doi:10.1155/2015/648108. [4] Draelos, Z. D. (2007). What are cosmeceutical peptides? Dermatology Times, 28(11). Retrieved from https://www.dermatologytimes.com/view/what-are-cosmeceutical-peptides [5] He B, Wang F, Qu L. Role of peptide-cell surface interactions in cosmetic peptide application. Front Pharmacol. 2023 Nov 13;14:1267765. doi: 10.3389/fphar.2023.1267765. PMID: 38027006; PMCID: PMC10679740. [6] 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. [7] 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. [8] Bae, S. H., et al. (2020). "Copper peptides as a potential therapeutic agent for skin aging." Journal of Cosmetic Dermatology, 19(9), 2245-2252. doi:10.1111/jocd.13435. [9] Zhao, Y., et al. (2019). "Peptides and Proteins as Skin Moisturizers." Cosmetics, 6(3), 32. doi:10.3390/cosmetics6030032. [10] International Journal of Cosmetic Science Skin permeability, a dismissed necessity for anti-wrinkle peptide performance Seyedeh Maryam Mortazavi, Hamid Reza Moghimi First published: 18 March 2022 https://doi.org/10.1111/ics.12770 [11] Lindgren, M., Hällbrink, M., Prochiantz, A., & Langel, Ü. (2000). Cell-penetrating peptides. Trends in Pharmacological Sciences, 21(3), 99-103. [12] Tripathi, P. P., Arami, H., Banga, I., Gupta, J., & Gandhi, S. (2018). Cell penetrating peptides in preclinical and clinical cancer diagnosis and therapy. Oncotarget, 9(98), 37252-37267. [13] Chu, D., Xu, W., Pan, R., Ding, Y., Sui, W., & Chen, P. (2015). Rational modification of oligoarginine for highly efficient siRNA delivery: structure-activity relationship and mechanism of intracellular trafficking of siRNA. Nanomedicine: Nanotechnology, Biology and Medicine, 11(2), 435-446. [14] Frankel, A. D., & Pabo, C. O. (1988). Cellular uptake of the tat protein from human immunodeficiency virus. Cell, 55(6), 1189-1193. [15] Guidotti, G., Brambilla, L., & Rossi, D. (2017). Cell-Penetrating Peptides: From Basic Research to Clinics. Trends in Pharmacological Sciences, 38(4), 406-424. [16] Zonari, A., et al. (2023) "Double-blind, vehicle-controlled clinical investigation of peptide OS-01." Journal of Cosmetic Dermatology. doi:10.1111/jocd.16242. [17] Kirkland, J. L., et al. (2017). "Cellular Senescence: A Key Regulator of Aging." *Nature Reviews Molecular Cell Biology*, 18(7), 473-485. doi:10.1038/nrm.2017.30. [18] Fang, E. F., et al. (2019). NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nature Communications, 10(1), 5284. [19] Chang CH, Tsai WC, Hsu YH, Pang JH. Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts. Molecules. 2014 Nov 19;19(11):19066-77. doi: 10.3390/molecules191119066. PMID: 25415472; PMCID: PMC6271067. [20] Resende, Diana I. S. P., Marta Salvador Ferreira, José Manuel Sousa-Lobo, Emília Sousa, and Isabel Filipa Almeida. 2021. "Usage of Synthetic Peptides in Cosmetics for Sensitive Skin" Pharmaceuticals 14, no. 8: 702. ![]() Age clocks are sophisticated tools designed to measure our biological age, which differs from chronological age. While chronological age simply counts the years since birth, biological age reflects the functional state of an individual's body or specific tissues, such as the skin. These clocks use various biomarkers to estimate how well a person's body is aging at a cellular and molecular level. Biological age is a more accurate indicator of health and longevity than chronological age. It can be influenced by factors such as genetics, lifestyle, diet, and environmental exposures. Two individuals or even identical twins of the same chronological age may have significantly different biological ages, highlighting differences in their overall health and susceptibility to age-related diseases. Measuring biological age offers several benefits: 1. Early detection of accelerated aging, allowing for timely interventions. 2. Personalized health recommendations based on individual aging profiles. 3. Monitoring the effectiveness of lifestyle changes and anti-aging interventions. 4. More accurate prediction of health risks and potential longevity. For the skin specifically, measuring biological age can help assess the impact of environmental factors like sun exposure and guide targeted skincare strategies. Overall, biological age measurements provide valuable insights into an individual's health status, enabling proactive steps towards improving healthspan and potentially extending lifespan. Microbiome-based aging clocks represent an innovative approach to estimating biological age by leveraging the dynamic changes in the human microbiome throughout life. This concept has gained significant attention in recent years due to the growing understanding of the gut microbiome's crucial role in health and aging processes. INTRODUCTION TO MICROBIOME-BASED AGING CLOCKS Microbiome-based aging clocks are predictive models that estimate biological age using the composition, diversity, and functionality of the gut microbiota. These clocks offer a novel perspective on aging, complementing traditional epigenetic and other biological age clocks. COMPARISON WITH OTHER BIOLOGICAL AGE CLOCKS Epigenetic age clocks Epigenetic clocks, based on DNA methylation patterns, have been widely used to estimate biological age. These clocks, such as Horvath's clock and GrimAge, analyze specific CpG sites to predict age with high accuracy across various tissues including skin. OTHER BIOLOGICAL AGE CLOCKS ▌Telomere length-based clocks: Measure the length of telomeres, which shorten with age. ▌Proteomic clocks: Analyze protein levels in blood to estimate biological age. ▌Transcriptomic clocks: Use gene expression patterns to predict age. Compared to these established clocks, microbiome-based aging clocks offer unique advantages: 1. Non-invasive sampling: Gut microbiome samples can be collected easily through stool samples. 2. Rapid modulation: The microbiome can be quickly altered through diet and lifestyle changes, allowing for potential interventions. 3. Functional insights: These clocks provide information on metabolic and immune functions related to aging. TYPES OF MICROBIOME-BASED AGING CLOCKS Microbiome-based diversity clock: This model links the loss of microbial diversity to increased frailty. The 'Hybrid Niche Nature Model' uses Hubbell’s diversity index to estimate healthy aging, focusing on rare and abundant species rather than traditional richness and evenness measures. Although theoretical, this model suggests that greater uniqueness in the gut microbiome correlates with better health outcomes in older adults. Taxonomic composition-based clocks: These clocks predict age by analyzing the relative abundance of bacterial taxa at various levels. Machine learning models trained on large datasets can predict age with varying accuracy. For example, a study using gut microbiome data achieved a mean absolute error of 5.91 years. Another study found that skin microbiomes were more accurate than gut microbiomes in predicting age. Functional capacity-based clocks: These clocks assess the functional capacity of the microbiome by examining genes or metabolic pathways involved in microbial functions. They offer consistency across cohorts by focusing on microbial functions as a common denominator of health. A recent study developed a functional clock with a mean absolute error of 12.98 years by analyzing meta-transcriptomic profiles from a large cohort. Metabolite-based clocks: While still in development, these clocks use microbe-associated metabolites as biomarkers for biological age. Secondary bile acids, abundant in centenarians, have been identified as potential indicators. Multi-omics-based clocks: By integrating metagenomics, metatranscriptomics, and metabolomics data, these clocks provide a comprehensive understanding of the microbiome's role in aging. A study combining taxonomic and functional data achieved an average mean absolute error of 8.33 years. Microbiome-based aging clocks are promising tools for measuring biological aging and guiding health interventions. Their responsiveness to lifestyle changes makes them ideal for assessing strategies to promote longevity. As research progresses, combining host and microbiome data could enhance the accuracy of biological age predictions. This integrated approach will deepen our understanding of aging and help evaluate treatment effectiveness. Ultimately, these innovative tools will support a personalized approach to healthy aging, enabling dynamic precision skincare routines and lifestyle choices based on our unique biological profile. Take care Anne-Marie REFERENCES 1. Biological age vs. chronological age: ▌Belsky DW, et al. Biological age is superior to chronological age in predicting hospital mortality among critically ill patients. J Am Geriatr Soc. 2023;71(8):2462-2470. doi:10.1111/jgs.17982. 2. Health and longevity: ▌Levine ME, et al. DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol. 2015;16:25. doi:10.1186/s13059-015-0584-6. 3. Personalized health recommendations: ▌Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14:R115. doi:10.1186/gb-2013-14-10-r115. 4. Monitoring effectiveness of interventions: ▌ Zhang Y, et al. Biological age estimation: methods and biomarkers. Front Public Health. 2023;11:1074274. doi:10.3389/fpubh.2023.1074274. 5. Skin and environmental factors: ▌Richie J, et al. Skin photoageing following sun exposure is associated with decreased epigenetic and biologic age. Br J Dermatol. 2024;190(4):590-592. doi:10.1093/bjd/ljad527. 6. Microbiome's role in aging: ▌Ghosh T, et al. The gut microbiome as a modulator of healthy ageing. Nat Rev Gastroenterol Hepatol. 2022;19(8):497-511. doi:10.1038/s41575-022-00605-x. 7. Microbiome-based aging clocks: ▌Liu Z, et al. Human gut microbiome aging clocks based on taxonomic and functional profiles. Microbiome. 2022;10(1):1-15. doi:10.1186/s40168-022-01275-5. 8. Epigenetic age clocks: ▌Horvath S, et al. The epigenetic clock as a biomarker of aging and longevity: a review of recent advances and future directions. Aging Cell. 2022;21(9):e13607. doi:10.1111/acel.13607. 9. Microbiome-based diversity clock: ▌Sala C, et al. Gut microbiota ecology: Biodiversity estimated from hybrid neutral models and its relationship with health. PLoS One. 2020;15(10):e0237207. doi:10.1371/journal.pone.0237207. 10. Functional capacity-based clocks: ▌Min M, Egli C, Sivamani RK. The gut and skin microbiome and its association with aging clocks. Int J Mol Sci. 2024;25(13):7471. doi:10.3390/ijms25137471. 11. Taxonomic composition-based clocks: ▌Liu Y, et al. A biological age clock based on microbiome composition and its application in health assessment among older adults: an observational study in the UK Biobank cohort study population (N=500,000). Lancet Healthy Longev. 2023;4(7):e465-e466.doi:10.1016/S2666-7568(23)00213-1. 12. Metabolite-based clocks: ▌Sato Y, et al., Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians, Nature. 2021;599(7885):458–464.doi:10.1038/s41586-021-03832-5. |
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