Skin Pores – Reducing Their Size

Many endogenous and exogenous factors are known to cause enlarged pilosebaceous pores. Such factors include sex, ageing, diet, chronic ultraviolet light exposure, comedogenic xenobiotics, acne, genetic and epigenetic predisposition, and seborrhoea. Most of these causative factors of enlarged pores, being exogenous and controlled by enironmental factors, means you can do something about it. There are procedures and topical products you can use to reduce pore size.

From: Yousef et al (2024)

Although the pathogenesis of enlarged facial pores is still not fully understood, three factors are thought to be key to the pathology: 1) high sebum production, 2) decreased skin elasticity around pores, and 3) increased hair follicle volume. Other factors, including chronic recurrent acne, diet, sex hormones, and skin care regimens, such as inappropriate use of cosmetics, modern Western diets, washing habits, and sun exposure, also affect pore enlargement. Many of these factors will affect the epigenetics of the skin and therefore the skin’s health and potentially pore size. Epigenetics are regulated by your environment, so there is much you can do to reduce enlarged pores.

Causes of Large Pore Size

In cross-sectioned images of conspicuous, enlarged pores, a strongly undulated epidermal–dermal junction was commonly observed around a pore’s opening. Areas with this feature correlated well to the areas with larger hollows and an uneven skin tone. (Sugata et al, 2007).

Recent clinical studies have confirmed the cause of facial pore size to be multifactorial. A positive correlation of pore size and number with sebum output level has been confirmed by several studies (Roh et al, 2006; Kim et al, 2013). Enlarged pores increase with age, up to 40 years, and then stabilize or only slightly increase (Jung et al, 2018). Another significant correlation was detected between skin elasticity and pore number in two independent studies suggesting that the structure of dermis could be involved in pore widening (Kim et al, 2013; Hameed et al, 2019). Other observations found pore counts were related to wrinkle severity; and the loss of Microfibril-associated glycoprotein-1 in the hair follicle/pore area with aging and photo-exposure, indicating a lack of matrix support in the dermis (Zheng et al, 2013; Jung et al, 2018).

Both epidermal and dermal structual impairments have been identified as a cause of large pores. Microscopic imaging of pores revealed inner structural changes affecting skin, including a lower density of collagen in the deeper dermis, a thicker stroma and coarser collagen fibers forming a tubular structure around the follicle, and an irregular basement membrane ultrastructure, all of which may result in an altered distribution of skin tensions (Sugata et al, 2008;  Sugiyama-Nakagiri et al, 2008; Mizukoshi and Takahashi, 2014). These ultrastructural alterations may result from inflammation, and recent data suggest inflammaging, mediated by complement activation (immune system proteins), as one of the possible inflammatory agents in the formation of enlarged facial pores (Qiu et al, 2024). Bacteria, such as Staphlacoccus aureus, infect hair follicles and pores, and the question remains, does the inflammation with this sort of infection enlarge the pore. Defects in epidermal morphology around pores have also been discovered, such as epidermis thickening and acanthosis (thickening of the stratum spinosum layer), likely indicating abnormal and possibly excessive keratinocyte proliferation ( Mizukoshi and Takahashi, 2014).

Procedures to Reuce Pore Size

Procedures, such as Micro-focused ultrasound with visualization (MFU-V), have been found to reduce pore size. MFU-V uses focused ultrasound energy to lift and tighten the skin by delivering heat to specific tissue layers beneath the skin’s surface, stimulating collagen production and causing skin tightening according to The Journal of Clinical and Aesthetic Dermatology. The visualization aspect of the procedure allows practitioners to see the underlying tissue during treatment, ensuring precise targeting and optimal results.

Topical S2RM to Reduce Pore Size – It’s Not Just the Exosome, It’s the Secretome

But are procedures needed to reduce pore size? No, the right choice of topical skin care products can significantly reduce pore size too. The secretome from adipose mesenchymal stem cells, something used in the NeoGenesis S2RM technology, significantly reduces pore size. That inflammation inducing the ultrastructual changes causing pores to enlarge can be reduced- reduce the inflammation with ADSC secretome found in the NeoGenesis S2RM technology. Remember, It’s Not Just the Exosome, It’s the Secretome that is optimal for reducing inflammation and regenerating tissue – including the tissue that constructs the pore. Changes of TEWL found that ADSC secretome can faciltate the recovery of the skin barrier function (Zhou et al, 2013), which can be explained by ADSC secretome normalizing the proliferation and migration of human primary keratinocytes as reported by Moon et al (2012). Both the epidermis (Ren et al, 2024) and dermis (Silveira et al, 2022) and hypodermis (An et al, 2021) are regenerated by ADSC secretome, with ADSC secretome containing collagen type IV needed to build the basment membrane, thereby regulating that “undulated epidermal–dermal junction” found to underly increased pore size.

I want to emphasie that inflammaging, inflammation that occurs as we age, is exposome induced. Those who eat well and live in an healthy envionment don’t suffer from inflammaging (Franck et al, 2025). As Franck et al write, “Inflammaging, as measured in this manner in these cohorts, thus appears to be largely a byproduct of industrialized lifestyles, with major variation across environments and populations.” In other words, if you live a healthy lifestyle, chronic inflammation, including inflammaging, is something you won’t suffer. This will reflect in your skin health, and your skin’s pore size.

Summary

Pore size in the skin depends on your envionment, your so-called exposome. Healthy skin is beautiful skin, including beautiful, healthy pores. Eat well to keep the skin healthy with sebum production levels normal and therefore reducing a risk factor for increased pore size. And the right choice of topical skin care products can help keep the skin healthy and pore size normal.

NeoGenesis’ New Vitamin C Product – Vibrant C Serum – Why It’s Different and Better

There are many topical vitamin C products on the market, but I needed to formulate something new because the other products are suboptimal for a number of reasons that I discuss here. Some Vitamin C products feature too much Vitamin C (15-20%) that inhibits elastin, and include alcohol at high levels to disrupt the skin barrier (penetration enhncement), resulting in the induction of inflammation in as little as 3 days of use. Alcohol-induced penetration across the skin is the result, at least in part, of stratum corneum intercellular lipid removal – in other words, alcohol destroys the fats in the skin’s barrier. Liposomal ascorbic acid is one reason the NeoGenesis vitamin C product, Vibrant C Serum, is better, and our built-in antioxidant cascade system is another. Unlike alcohol-based products with high levels of ascorbic acid (20% product and a 15% product; notice too that both of these products contain phenoxyethanol that kills cells), NeoGenesis’s Vitamin C product doesn’t destroy the skin’s barrier and doesn’t inhibit elastin, nor does it kill epithelial cells like some other Vitamin C products..

Primates, including humans, cannot synthesize vitamin C. Most other mammals (except guinea pigs), including our cats and dogs, can produce vitamin C, but primates have lost this ability due to a beneficial genetic mutation. Primates evolved to eat mostly, if not exclusively, plants and therefore obtained all the vitamin C they needed through their diets. Look at those big, strong Gorillas, they eat only plants. We primates evolved to eat plants, loaded with C, all that we needed for optimal health, and so we eventually lost the genetics to make vitamin C. In other words, we mutated, and that pesky DNA sequence for making vitamin C was a waste of energy and therefore to be efficient, evolution of primates dropped the unneeded sequence. Pretty cool how mother nature is so efficient and evolution is such as great designer, doing so without a designer. Thinking teleogically, what she said was, “you eat so much vitamin C, you don’t need to make it anymore.”

Reasons Why the Skin May Not Have Adequate Vitamin C Levels

But that was then, and this is now. People don’t eat so well these days and are stressed-out, both of which can lead to suboptimal levels of vitamin C in the skin. Even if you eat sufficent levels of Vitamin C, the transporters of vitamin C from the blood vessels don’t work well under conditions of chronic inflammation – therefore those with chronic inflammation in the skin may not be receiving adequate levels of dietary vitaimin C required for both dermal and epidermal function. The blood vessels bringing the vitamin C to the skin are no longer transporting it out of the blood into the skin – the process has been decommissoned by inflammation in the skin.

Ascorbic Acid (Vitamin C) Doesn’t Easily Penetrate the Skin

Vitaimin C (VC) has a molecular weight of only 176.12 g/mol, but it is a hydrophillic small molecule and because it interacts with water and not lipids, it dosen’t penetrate the fatty stratum coreum very well. Many companies put high levels of VC in their products, but the VC just lays on the surface of the skin.

High Levels of Vitamin C on the Skin’s Surface Oxidize (DHA an Anti-inflammatory) But Still Provide No Benefit

That 15% VC product you’re using may just sit on the surface of your skin where it will oxidize. Dehydroascorbic acid (DHA) is the oxidized form of VC, and it too has anti-inflammatory benefits just as VC does. If only it would penetrate the skin and provide benefit. Oxidized VC in the DHA form has benefits and cells, such as keratinocytes, readily take up DHA to convert it back to VC, but it needs to penetrate to the cells (keratinocytes) in the skin to give benefit. If the DHA sits on the surface of the skin too long, it can further breakdown to oxalic acid that can irritate the skin.

For those who would like to know, DHA is reduced to ascorbic acid by cytosolic reductases GSH-NADPH-dependent, lipoic acid-NADH-dependent, and thioredoxin reductase. The bottom line is that both AA and DHA are important to the skin, but longer term oxidation of AA and DHA into oxalic acid is likely detrimental.

Liposomes Carry Vitamin C Into the Skin

You’ll notice lecithin as part of the ingredient list on the Vibrant C Serum. Lecithin is part of the ingredient combination involved in making the liposomes that encapsulate the ascorbic acid. The liposomes not only protect the ascorbic acid, but importantly, carry the ascorbic acid through the stratum corneum to the deeper layers of the skin. The liposomes act without disrupting the stratum corneum and epithelial barrier function. This is different from some other Vitamin C skin care products that use alcohol as a penetration enhancer. Alcohol, especially at high concentrations, disrupts the lipid structure of the stratum corneum and reduces barrier function.

For example, some products use 15% ascorbic acid, along with an alcohol called Ethoxydiglycol, a type of ethanol. They use over 15% alcohol in their formula because the ethoxydiglycol is listed before the ascorbic acid on the product’s ingredient list – this alcohol is used as a penetration enhancer and using a high level of this alcohol in the formulation can disrupt the corneum stratum and induce irritation. In other words, this product is disrupting the stratum corneum’s barrier function.

Positive Epigenetic and Cellular Effects of Vitamin C Once It’s Absorbed Into the Skin

When VC penetrates to the keratinocytes, remarkable and beneficial physiological processes occur.  VC increases epidermal thickness by promoting keratinocyte proliferation through the DNA demethylation of proliferation-related genes (Sato et al, 2025). This is an epigenetic effect, where VC helps to remove a methyl group that is attached to the DNA in the keratinocyte, so-called demethylation, and this allows the keratinocyte to proliferate. Part of what happens in life is that some of our DNA accumulates methyl group attachements, something that can “turn-off” the DNA. VC demethylates the DNA and turns it on again, allowing the keratinocyte to once again proliferate. It’s much more complicated than this, but for the keratinocytes this is the basic hypotheisis that scientists have brought forth.

In terms of the epidermis, L-ascorbic acid (vitamin C [VC]) is widely recognized for its antioxidant properties in the skin (Masaki, 2010), enhances collagen synthesis (Kishimoto et al, 2013), alleviates UV-induced damage to the epidermis (Kawashima et al, 2018), and inhibits melanin deposition (Sato et al, 2017). Long-term VC deficiency leads to epidermal atrophy in a mouse model with disrupted VC synthesis capabilities (Sato et al, 2012). VC promotes keratinocyte viability, induced expression of differentiation marker genes, and increased SC barrier lipids in monolayer or organotypic cultures of normal human keratinocytes (Boyce et al, 2002; Michalak et al, 2021). Together, these data suggest that VC is critical to epidermal cell proliferation and differentiation.

Collagen and Matrix Formation

Vitamin C is also crucial for the production of collagen, a protein that helps to form your skin’s overall structure and barrier and enhances your skin’s elasticity. Collagen is an important building block of the skin. In addition to stabilising the collagen molecule by hydroxylation, vitamin C also stimulates collagen mRNA production by fibroblasts in the dermis yiedling more collagen and stable collagen. Hydroxylation of collagen is a critical post-translational modification where specific amino acids, proline and lysine residues, are hydroxylated, forming hydroxyproline and hydroxylysine, respectively. This process is vital for collagen’s structural integrity, stability, and proper function, particularly within the extracellular matrix. So, Vitamin C helps to stabilize the collagen that is present, as well as to help produce new collagen.

Skin collagen is a long-lived protein, having a long half-life that is estimated to be approximately 15 years, so some skin collagen can exist for much of your life. In young, healthy skin, the amount of enzymes, such as MMP (proteases) that breaks down collagen is low, and therefore, collagen degrades very slowly. However, as we age and more MMP is present, collagen ages, it starts to degrade and fragment. Unfortunately, the degraded and fragmented collagen cannot be incorporated into new collagen fibers and it accumulates within the extracellular matrix of the dermis. The presence of fragmented collagen remainders in aged dermis inhibits both fibroblast proliferation and type I procollagen synthesis by these cells, further degrading the dermis. 

It’s the supporting matrix, such as collagen and elastin, that gives the skin its tightness, thickness, and firmness, but over the years, it starts to break down. That’s why skin gets saggy and thin. Again, Vitamin C is one factor, a necessary factor, to protect collagen and to produce new collagen.

Using the Optimal Amount of Ascorbic Acid: Too Much Vitamin C Inhibits Elastin

Elastin helps form the dermal matrix and helps give elasticity to the skin. Like collagen, much of the eleastin is formed in the dermis by fibroblasts. Differential effects of ascorbic acid on collagen I and elastin mRNA abundance result from the combined, marked stabilization of collagen mRNA, the lesser stability of elastin mRNA, and the significant repression of elastin gene transcription. In other words, too much Vitamin C can inhibit elastic production. At NeoGenesis, we use a topical 5% of ascorbic acid, the natural form of Vitamin C, that has been found by scientists at major university in France to rebuld the skin’s ultratructure and provide clincially visible benefits to the skin, rebuilding collagen but not destroying elastin. Moreover, our stem cell-based S2RM technology stimulates fibroblasts to form collagen and elastin, a perfect complement to our Vitamin C product..

Notice we at NeoGenesis don’t use sodium ascorbate because sodium accululates in the skin and induces inflammation, including in skin conditions such as psoraisis and autoimmune diseases. Skin sodium content has been positively and significantly correlated with classical inflammatory markers such as CRP and white blood cell count. For example, dietary salt loading can result in hypertonic sodium storage in the skin by binding to glycosaminoglycans. Topical sodium can add to the accumulation, so wherever possible, we don’t use sodium molecules in our NeoGenesis formulations.

Antioxidant Cascade – Primary and Seconday Antioxidants

You’ll find a number of primary and secondary antioxidants (they work indirectly to prevent oxidation) in the Vibrant C Serum, including: Rose Geranium (Pelargonium spp.) water, Ascorbic Acid, Magnesium Ascorbyl Phosphate, Gluconolactone, Ferulic Acid, Panthenol (a secondary antioxidant), Resveratrol, Sodium Benzoate, Hydrolyzed Rice Protein, Potassium Ascorbyl Tocopheryl Phosphate, Chinese Senna (Cassia Obtusifolia) Seed Extract, Glutathione, Curcumin (encapsulated), Honokiol, Magnolol, Ergothioneine, Soybean (Glycine Soja) Protein, and Superoxide Dismutase.

The antioxidant cascade is a series of reactions where one antioxidant molecule neutralizes a free radical and, in doing so, becomes oxidized itself. This oxidized antioxidant can then be recycled back to its active, reduced state by another antioxidant, and so on, creating a chain reaction that efficiently eliminates harmful free radicals. Antioxidants working in a cascade is where one antioxidant type regenerates another type. For example, vitamin E neutralizes lipid radicals but becomes a radical itself; vitamin C can then restore vitamin E to its active form. Enzymatic antioxidants like SOD, CAT, and GPx (Glutathione peroxidase family of enzymes) handle different reactive species at various cellular locations, creating a layered defense This process helps maintain cellular redox balance and protect against oxidative stress. Thus, different types of antioxidants work together in a cascade process by complementing, supporting, and regenerating each other’s activity, resulting in a more robust and comprehensive defense against oxidative stress than any single antioxidant could provide alone. The pathways in cellular oxidation and antioxidation are complex, involving many pathways and may different types of antioxidants. While vitamin C is important, having the other antioxidants available concurrently is critical to the cellular redox balance, the the dynamic equilibrium within a cell between oxidation and reduction reactions. Both are critical to normal cellular function.

Summary

The antioxidant cascade, involving many antioxidant types, not just Vitamin C, is important for neutralizing free radicals, but also very important in regulating cellular signaling, gene expression, and repair mechanisms. Antioxidants, such as the encapsulated curcumin found in Vibrant C Serum, can modulate key pathways (like NF-κB and MAPK) to reduce inflammation and enhance cell survival and regeneration. Delivering these many antioxidants to the cells in the skin where they can provide benefit requires good formulations where, for example, liposome and encapsulation delivery technologies are used by NeoGenesis for its Vibrant C Serum product.

Why NeoGenesis Uses Sodium Benzoate and Gluconolactone As An Antimicrobial Preservative System

The use of gluconolactone and sodium benzoate together as a preservative system has, 1.  a wide range of global regulatory acceptance, 2. Broad spectrum antimicrobial activity, 3.  ECOCERT/COSMOS-accepted. 4.NATRUE- approved and Soil Association-approved, 5. added moisturization benefit, and 6. anti-inflammatory properties. This safe and efficacious preservative system with skin benefits compares to others such as phenoxyethanol that is toxic and easily penetrates the skin into the blood.

Sodium Benzoate

Cinnamon contains a major compound, cinnamaldehyde, which is converted into cinnamic acid by oxidation. In the liver, this cinnamic acid is β-oxidized to benzoate (Abd El-Mawla et al., 2001) that exists as sodium salt (NaB) or benzoyl-CoA. As a safe metabolite of cinnamon, sodium benzoate (NaB), is a widely-used food preservative and a FDA-approved drug against urea cycle disorders in humans, found to increase the levels of neurotrophic factors [e.g., brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3)] in the CNS (Jana et al, 2013). So safe is NaB that it is approved as an injectable for certain brain diseases (Misel et al, 2013).

NaB is of medical importance as it is a component of Ucephan, a FDA-approved drug used in the treatment for hepatic metabolic defects associated with hyperammonemia such as urea cycle disorder in children (Leonard and Morris, 2002; Scaglia et al., 2004). It is also widely used as a preservative in broad range of foods and cosmetic products (Nair, 2001). It is non-toxic and can be administered as a solution in drinking water. One study reported that a 2% solution of NaB in drinking water is safe for lifelong treatment in mice without any measurable negative side effects (Toth, 1984). Recent studies have found that NaB is capable of modulating both innate and adaptive immune responses (Brahmachari and Pahan, 2007; Brahmachari et al., 2009; Brahmachari and Pahan, 2010), several studies finding that NaB in switching the balance of Th cell subsets toward anti-inflammatory Th2 and Tregs types (Brahmachari et al, 2007; Rezaei et al, 2016). Inflammatory cytokines found in arthritis were also found to be decreased with NaB using in vitro models (Bemani et al, 2020).

NaB is not only efficacious as an antimicrobial preservative and as an immune modulator, but it is also safe – it does not convert to benzene under the conditions of use as a cosmetic or food preservative as told by some ignorent people I’ve heard talk about the subject. This was a concern back in the 1990s, but was cleared as a problem in the 2000s. Those initial reports from the FDA that small amounts of benzene were in soda drinks has now been found to be in error, as the FDA has said, “the TDS [FDA’s Total Diet Study lab] benzene results appeared to be unreliable.” Benzene formation in the analytic techniques used by the FDA’s TDS lab in Kansas were the culprit, along with contamination (FDA Report, 02/25/2022).

Gluconolactone

In nature, GLA can be found in honey, tofu, cheese, wine, bread, fruit juices, among others, and as an approved food additive

Gluconolactone (GDL) is anti-inflammatory by enhancing in vitro induced (i)Treg differentiation and function, and in imiquimod-induced autoimmunity in mice, treatment with GDL alleviates inflammation by inhibiting TH17 cells (Li et al, 2025).

In patients suffering from cutaneous lupus erythematosus, topical application of a GDL-containing cream controlled skin inflammation and improved the clinical and histologic appearance of the skin lesions within 2 weeks (Li et al, 2025).

GLA exhibits antioxidant and moisturizing effects. It protects elastin fibers from UV-induced degradation (Jarząbek-Perz et al, 2023).

NaB and GLA Compared to Phenoxyethanol

Compared to anti-inflammatory and non-toxic NaB and GLA, phenoxyethanol (PE) is known to be toxic to epithelial cells (Wang et al, 2020). At concentrations equal to and/or less than those dosages approved for human use, PE significantly decreased the signaling activity of the Akt pathway in epithelial cells within 30 min, and induced their atrophy and death within 24 h of exposure. Further, PE is known to penetrate the skin when topically applied, having a dermal resorption rate of about 45% in humans – meaning 45% of PE applied topically travels through the skin into the blood (Eckert et al, 2025).

Summary

The use of gluconolactone and sodium benzoate together as an antimicrobial preservative system for skin care not only provides safe and effective, broad-spectrum effects, the combination also provides substantial skin care benefits, including moisturization, UV protection, and anti-inflammatory effects. Carefully choosing every ingredient we put into our products is one reason why NeoGenesis products are safe and efficacious.

References

Abd El-Mawla AM, Schmidt W, Beerhues L. Cinnamic acid is a precursor of benzoic acids in cell cultures of Hypericum androsaemum L. but not in cell cultures of Centaurium erythraea RAFN. Planta. 2001;212:288–293.

Brahmachari S et al (2007) Sodium Benzoate, a Food Additive and a Metabolite of Cinnamon, Modifies T Cells at Multiple Steps and Inhibits Adoptive Transfer of Experimental Allergic Encephalomyelitis1. J Immunol 1 July 2007; 179 (1): 275–283.

Bemani P et al (2020) In Vitro Effects of Sodium Benzoate on the Expression of T Cells-related Cytokines and Transcription Factors in Adjuvant-induced Arthritis Model. Iran J Allergy Asthma Immunol, May2020; 19(Supple.1):43-54.

Eckert E, Jäger T, Leibold E, Bader M, Göen T, Hiller J. Dermal penetration of 2-phenoxyethanol in humans: in vivo metabolism and toxicokinetics. Arch Toxicol. 2025 Mar;99(3):1095-1103.

Jarząbek-Perz S, Dziedzic M, Rotsztejn H, Kołodziejczak A. Evaluation of the effects of 10% and 30% gluconolactone chemical peel on sebum, pH, and TEWL. J Cosmet Dermatol. 2023; 22: 3305-3312.

Li W et al (2025) Gluconolactone restores immune regulation and alleviates skin inflammation in lupus-prone mice and in patients with cutaneous lupus.Sci. Transl. Med.17,eadp4447(2025).

Jana A, Modi KK, Roy A, Anderson JA, van Breemen RB, Pahan K. Up-regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: therapeutic implications for neurodegenerative disorders. J Neuroimmune Pharmacol. 2013 Jun;8(3):739-55.

Misel ML, Gish RG, Patton H, Mendler M. Sodium benzoate for treatment of hepatic encephalopathy. Gastroenterol Hepatol (N Y). 2013 Apr;9(4):219-27

Rezaei N, Amirghofran Z, Nikseresht A, Ashjazade N, Zoghi S, Tahvili S, Kamali-Sarvestani E. In Vitro Effects of Sodium Benzoate on Th1/Th2 Deviation in Patients with Multiple Sclerosis. Immunol Invest. 2016 Oct;45(7):679-91.

Wang J, Yang Liu, Wendy R. Kam, Ying Li, David A. Sullivan, Toxicity of the cosmetic preservatives parabens, phenoxyethanol and chlorphenesin on human meibomian gland epithelial cells, Experimental Eye Research, Volume 196, 2020, 108057,

Synthetic Peptides are the Rage in Skincare – Too Bad Most Don’t Work Well

Scientists have known for decades about the benefits of natual peptides derived from our diets. However, topically applied synthetic peptides are easily broken down in the skin and have considerable difficulty penetratring the stratum corneum, both of which degrade their bioactivity. Some peptides have a high molecular weight, many are hydrophilic in character, and are highly susceptibility to enzymatic degradation, requiring the application of formulation technologies to improve the stability and the penetration of peptides through the skin. On the other hand, natural peptides produced by the human body have developed protection and functional mechanisms. If you’re using S2RM from NeoGenesis, you’re using these natually produced peptides. Learning lessons from mother nature, a few science-based companies have followed nature and are attempting to develop biomemetic peptides that are “protected and functional peptides.” Too bad most cosmetic companies don’t know about and don’t use these “protected and functional peptides.”

Written in the journal, Future Drug Discovery, “Peptides have traditionally been perceived as poor drug candidates due to unfavorable characteristics mainly regarding their pharmacokinetic behavior, including plasma stability, membrane permeability and circulation half-life” (Christina Lambers, 2022).

Peptides, along with exosomes, are “one of the skincare industry’s favorite ingredients right now,” Vogue reported in December 2024. At a Clinique launch event in early 2024, a physician declared peptides to be “the buzzword of the year.” The fashion of peptides seems to be at its peak hype (Fig.1): “Skincare is in its peptides era,” the beauty and fashion website Hypebae announced last month. As I am often asked about peptides, and because most of the literature for the lay public about peptides is incomplete and just plain wrong, I offer my short intro to peptides here. My blog is “sciencey” because it has to be in order not to present peptides in a manner that is not superficial and presents simplified dross.

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From Maguire (2016)

What are peptides?

Basically, they’re short strings of amino acids (less than 50 amino acids). By contrast, proteins are long strings of amino acids. Peptides can be naturally produced or synthetically made in a laboratory. Naturally produced peptides are synthesized in the body as large precursor molecules (i.e., preproproteins) and are post-translationally (after the proprotein is made) processed and cleaved by proteases to generate their active peptide product. Synthetic peptides are typically made in the lab using a solid-phase peptide synthesis process where one amino acid at time is added to the string.

Problems with Synthetic Peptides

Synthetic peptides have many issues: off target activation of pathways that are detrimental to human health, poor targeting of beneficial pathways, poor penetration, and rapid degradation. Further, these synthetic peptides typically undergo lyophilization, a harsh freeze-druing process that disrupts their structure and further disrupts their safety and efficacy. Peptide aggregation and consequent loss of function is one of many problems in using synthetic peptides.

Further, the chemical synthesis process used to create peptides may introduce impurities or byproducts that can potentially lead to adverse reactions and toxicity issues. As stated in a journal from the American Chemical Society, “the current state of the art in peptide synthesis [synthetic peptides] involves primarily legacy technologies with use of large amounts of highly hazardous reagents and solvents and little focus on green chemistry and engineering” (Isidro-Llobet et al, 2019). Further, Varnava et al (2019) report that, “To date, the synthesis of peptides is concurrent with the production of enormous amounts of toxic waste.” In other words, the current industrial-scale peptide synthesis methods involve using substantial quantities of hazardous reagents and solvents, some of which may contaminate your topical product, while much of it pollutes the environment.

Synthetic peptides are cheap to make, and can easily be made in large quantities. That’s a plus for the compnies making them. But synthetic peptides can be problematic for therapeutic interactions that require post-translational modifications that are difficult to incorporate synthetically, such as glycosylation, for biological activity. Difficult to create disulfide linkages, important for the functional attributes of peptides and proteins. And peptides lack efficacy in biochemical pathways where the secondary or tertiary structure is critical or in making larger bioactive peptides and proteins. Natural peptides and proteins don’t suffer from these problems.

Microproteins ( you haven’t heard about these because they’re newly disovered) are Different from Peptides

You haven’t heard about these small proteins because they’re newly discovered and very difficult to identify and characterize. Microproteins are typically less than 100 amino acids (AAs) in length, but are different from peptides because they are not cleaved from a proprotein or protein. Until recently, microproteins have evaded detection because traditional genome annotation methods relied on stringent rules to distinguish protein coding RNAs versus non-coding RNAs (ncRNAs) to minimize the discovery of false positives including a minimum ORF length of 300 base pairs (bps). This ad hoc 100-codon threshold was initially selected based on the calculated probability that ORFs over 300 bps are significantly more likely to encode stable proteins. sORF-encoded microproteins have emerged as important new players in cellular biology and physiology, and they continue to be identified at high rates. To be clear, microproteins are polypeptides originating from short open reading frames (sORF) of less than a hundred codons. For a long time, they have been understudied because it is difficult to distinguish coding from non-coding sORFs. In recent years, the number of putatively translated sORFs has been narrowed down from hundred-thousands or millions to various thousands, owing to the advent of ribosome profiling and advances in bioinformatic and proteomic techniques. Therefore, efforts are now being made to include sORFs with robust translation evidence into databases such as GENCODE. The field of microproteins has since steadily grown, though it is still unclear how many functional coding sORFs exist in the human genome, and relatively few microproteins have been characterized to date. 

Microproteins are made in adipose mesenchymal stem cells (ADSCs) and likely released for therapeutic effect by the ADSCs (Bonilauri et al, 2021). Because of the past difficulty in identifying these microproteins, they are just now receiving attention for their therapeutic value. Understand, microproteins likely provide therapeutic value to the ADSC secretome, but our understanding of this is in its infancy.

Natural Peptides Drived from Diet

Lunasin is a 43-amino acid polypeptide originally discovered in soy. Research into the properties of lunasin began in 1996, when researchers at the University of California-Berkeley observed that the peptide arrested mitosis in cancer cells by binding to the cell’s chromatin and breaking the cell apart. The name of the peptide was chosen from the Tagalog word lunas, which means “cure”. Since its discovery, scientists have identified lunasin as the key to many of soy’s documented health benefits and it has been studied for various benefits, including cancer prevention, cholesterol management, anti-inflammation, skin health, and anti-aging. Lunasin exhibits different biological and chemopreventive properties including anti-inflammatory, anticarcinogenic, antioxidant and immune-modulating properties, anti-atherosclerosis, and osteoclastogenesis inhibition potential. Sounds great, right? But there’s a catch. Lunasin as part of a whole soy diet confers health benefits and is bioavailble, measured in human blood, but isolated lunasin has not shown such beneficial results. Isolated peptides don’t work as well as those peptides in their natural state. This is but one of many examples of natural peptides that are derived from a healthy diet providing benefit in their natural state, but when isolated, not so much happens.

Conjugated Peptides

The the human body, peptide conjugation is a crucial process involving the attachment of chemical entities to peptides to enhance their safety, efficacy, and pentration properties. These modifications, called post-translational modifications, can significantly improve characteristics like stability, targeting, and half-life of the peptide within the body, including the skin. Without peptide conjugation, the peptide is bare, subject to rapid degradation, and hydrophilic (meaning loves water and hates fat) so that it is repelled by the fatty nature of the stratum corneum. These are the problems with most synthetic peptides – they’re not conjugated. They’re not biomemetic but are cheap and can be easily hyped during the peak of the peptide-hype curve, i.e. peak of inflated expectation. However, synthetically conjugated peptides often don’t work well either.

For example, Palmitoyl Pentapeptide-4 is a conjugated peptide (pal-KTTKS). The molecular weight of Palmitoyl Pentapeptide-4 is 802.068 g/mol, larger than the “500 Dalton rule.” It consists of a pentapeptide (a chain of five amino acids, KTTKS) linked to a palmitoyl group, which is a fatty acid. This conjugation somewhat enhances its ability to penetrate the skin and makes it more effective as an anti-aging ingredient. However, Choi et al (2014) found that although pal-KTTKS was more stable than KTTKS, in dermal skin extract, 9.7% of pal-KTTKS remained after 120 min and 11.2% of pal-KTTKS remained at 60 min in the skin homogenate. In the epidermal skin extract, the concentration of pal-KTTKS throughout the 120-min incubation period was almost similar to its initial concentration. Lower amounts of proteolytic enzymes in the epidermal skin extract than in the dermal skin extract and the skin homogenate may account for pal-KTTKS lasting longer in the epidermal skin extract. 

Natural Proteins and Peptides Penetrate the Skin Better than Synthetic Peptides

Palmitoyl Pentapeptide-4 (PP-4), a conjugated peptide. Choi et al (2014) found only 11% of the peptide remains after 60 minutes in a homogenate of dermis – it’s broken down to be ineffective. Further, in skin permeation experiments, no detectable levels of KTTKS and pal-KTTKS (PP-4) were observed in the skin over a period of 48 h – the peptide dosen’t penetrate the skin.

Contrast this to the stem cell released molecules (Secretome) of ADSCs that do penentrate the skin and activate collagen production and a number of other beneficial physiological pathways. The secretome from ADSCs is loaded with proteins, peptides, microproteins, microRNA (not mRNA or DNA) and other beneficiary molecules. They work effectively, as mother nature intended, doing so collectively so that the mutlitude of molecules working togther, a systems therapeutic, exhibit synergistic, beneficial effects.

Summary

Synthetic peptides are all the rage now in skincare. Too bad most of them offer much hype and little or no benefit. There are some newer, more sophisticated conjugated peptides that I’m testing to determine whether they exhibit better efficacy than the current conjugated peptides. Stay tuned.

Safety and Efficacy: Adipose Mesenchymal Stem Cell (ADSC) Secretome Is Superior to Bone Marrow Mesenchymal Stem Cell (BMSC) and Umbilical Cord Mesenchymal Stem Cell (UCSC) Secretomes

I list here some of the reasons why I formulate my skin care products using the secretome of adipose mesenchymal stem cells (ADSCs) instead of bone marrow mesenchymal stem cells or umbilical cord mesenchymal stem cells. ADSCs are better at reducing inflammation and setting the innate and adaptive immune systems into a pro-regenerative state, inducing collagen formation, and laying down that collagen in a manner that is anti-fibrotic. This is a small excerpt of my upcomming peer-reviewed publication.

Listing Efficacy of ADSCs Versus BMSCs versus UCMSCs Secretome (Exosomes + Soluble Fraction)

Bone Marrow Mesenchymal Stem Cells (BMSCs), and the molecules they release, prolong and enhance inflammation by increasing survival and function of neutrophils (Casatella et al, 2011; Liang et al, 2024). BMSC secretome also reprograms hematopoietic stem cells to become inflammatory white blood cells (Ng et al, 2023). Under hypoxic conditions, which induces the activation of TRL4, BMSCs secrete pro-inflammatory factors and decrease the polarization of macrophages from the M1 to M2 phenotype, the M2 type being anti-inflammatory and therefore the BMSCs are promoting more inflammation (Faulknor et al, 2017; Waterman et al, 2010). Thus, BMSCs cultured in normal hypoxic conditions in the laboratory are secreting pro-inflammatory factors and when administered to wounded skin will induce inflammation by recruiting neutrophils and M1 type pro-inflammatory macrophages.
ADSCs have consistently exhibited much greater anti‑inflammatory capabilities, phagocytic activity, anti‑apoptotic capability activity and cell viability over BMSCs (Li et al, 2019).
ADSCs have been found to be highly immunomodulating cells, exceeding the suppressive effect of BMSCs by secreting more anti-inflammatory IL-6 and transforming growth factor-β1 (TGF-β1) Ceccarelli et al (2020).
When compared with the BMSCs- and UCSCs-treated groups, the ADSCs-treated group exhibited markedly accelerated healing efficiency, characterized by increased wound closure rates, enhanced angiogenesis, and collagen deposition at the wound site in an animal model (Cao et al, 2024).
ADSCs have biological advantages over BMSCs in the proliferative capacity, secreted proteins (basic fibroblast growth factor, interferon-γ, and insulin-like growth factor-1), and immunomodulatory, ant-inflammatory effects (Li et al, 2015).
Differences in cytokine secretion cause ADSCs to have more potent immunomodulatory effects than BMSCs (Melief et al, 2013)
ADSCs are better at preventing fibrosis than BMSCs (Yoshida et al, 2023).
Adipose mesenchymal stem cell secretome is superior to that of BMSCs because it preferentially helps to rebuild the epidermis by stimulating basal keratinocytes (Ademi et al, 2023).
BMSCs express much CTHRC1 protein (Turlo et al, 2023), which may help to promote fibrosis (Liu et al, 2023).
ADSC exosomes contain SIRT1 (Huang et al, 2020) and activate SIRT1 in other cells (Liu et al, 2021) to reduce inflammation, improve mitochondrial function, and reduce senescence.
ADSC exosomes reduce inflammation in endothelial cells (Heo and Kim, 2022).
ADSCs are considered more powerful suppressors of immune response than mesenchymal stem cells (MSCs) derived from different tissue sources, including trabecular bone, bone marrow, dental pulp, and umbilical cord (Ribeiro et al., 2013; Nancarrow-Lei et al., 2017).
 ADSCs immunomodulatory effects exceed that of BMSCs (Melief et al., 2013).
ADSCs secrete higher amount of immune suppressive cytokines, such as IL-6 and transforming growth factor-β1 (TGF-β1) than do BMSCs (Soleymaninejadian et al., 2012; Melief et al., 2013; Montespan et al., 2014).
Bochev et al (2008) showed that ADSCs had a stronger ability to inhibit immunoglobulin (Ig) production by B cells than BMSCs.
Ivanova-Todorova E et al (2009) found that Adipose tissue-derived mesenchymal stem cells are more potent suppressors of the adaptive immune response through limiting dendritic cells differentiation compared to bone marrow-derived mesenchymal stem cells.
ADSC secretome inhibits LPS-induced proinflammatory cytokines (Li et al, 2018)
Human ADSCs are key regulators of immune tolerance, with the capacity to suppress T cell and inflammatory responses and to induce the generation/activation of antigen-specific regulatory T cells (Gonzalez-Rey et al, 2010).
ADSC secretome can suppress the activation, proliferation, and function of CD8+ T cells, which are inflammatory killer T cells (Kuca-Warnawin et al, 2020).
ADSC secretome was able to elevate expression of M2 macrophages and modified their cytokine expression to an anti-inflammatory profile (Hu et al, 2016; Zomer et al, 2020)
Exosomes secreted by human adipose mesenchymal stem cells promote scarless cutaneous repair by regulating extracellular matrix remodeling (Wang et al, 2017).
ADSC exosomes reduce inflammation and alleviate keloids by promoting mitochondrial autophagy through the PI3K/AKT/mTOR pathway (Liu et al, 2024).
ADSC exosomes reduce injury through the transfer of mitochondria components to neighboring cells (Xia et al, 2022).
ADSC secretome expedited wound healing and reduced inflammation in an animal model (Ma et al, 2021).
ADSC secretome promotes wound healing without leaving visible scars and was found safe when injected (An et al, 2021).
ADSC secretome has positive effects on granulation tissue formation and vascularization, and helps prevent fibrosis in pressure ulcers (Alexandrushkina et al, 2020).
Human ADSCs secrete functional neprilysin-bound exosomes that can degrade β-amyloid peptide (Aβ) that is found in the skin – cutaneous amyloidosis (Katsuda et al, 2013; Kucheryavykh et al, 2018).
In psoriasis and eczema the secretome from adipose mesenchymal stem cells (ADSCs), can regulate SOCS (suppressor of cytokine signaling) pathways, and modulate JAK pathways to reduce inflammation (Wang et al, 2022; Ko et al, 2023). Further, the secretome from ADSCs increases SOCS3 expression and, thus, the persistent and uninhibited expression of STAT3 by increased SOCS3 effectively ameliorates tissue injury by promoting tissue regeneration and decreasing inflammation and apoptosis (Lee et al, 2016).
ADSC and BMSC secretomes were characterized by the upregulation of proteins linked to ECM structure and organization and proteolytic processes compared to UCSCs, important to active involvement in tissue repair and microenvironment maintenance and suggesting their advantage for tissue-forming applications (Hodgson-Garms et al, 2025), but ADSCs are better at preventing fibrosis and reducing inflammation (Yoshida et al, 2023).
Fu et al (2025) found that hADSC-Exos are more effective in promoting hair follicle development compared to hUCMSC-Exos, and the secretome of ADSCs was more associated with growth processes such as nucleosome function than was the UCMSC secretome (Fu et al, 2025).

AnteAge, Founded by a Physician Whose Medical License Was Revoked and is Now Owned by Private Equity, Invents Fake Technology

John Sanderson, whose medical license was revoked for sexual misconduct and repeated negligence, has sold his company, AnteAge, to a private equity company. Now that the PE company has taken over, their marketing people have invented a new word, “Biosome.” for what is called by scientists, a “liposome.”

How do we know the Private Equity guys who own AnteAge are using fake technology? Look at the staement from their website: “Currently the AnteAGE MD bottles do not mention the new Biosome ingredient. As part of our commitment to sustainability, we have chosen to utilize our existing inner packaging rather than generating waste unnecessarily. Please rest assured that your product does in fact have Biosomes included. Please reference the ingredient listing here. Reach out with questions or refer to anteage.com.”

Here’s the statment from their web:

How Do We Know They’re Faking It

If there were actually something new in the bottle, they would have to, by law, relable the product. In other words, because they have only changed their marketing hype, and not the product’s technology, they don’t need to make any changes to the bottle labeling – specifically the bottle’s listing of ingredients. The label and the ingredients remain the same and the only thing changing is what they call the product. There’s no validation in peer-reviewed literature or patent filings confirming a unique mechanism under the name “Biosome.” Rather, it’s just marketing hype, or as some would call it, BS.

So what’s in the bottle? Liposomes. Look at the ingredients on the bottles with the new, fake technology. The list includes “Phosphatidylcholine.” Guess what are made with Phosphatidylcholine. Answer – liposomes! So now AnteAge is calling liposome, you guessed it, Biosomes. This is Private Equity at work. Say anything, do anything, for profit.

Here’s the bottle saying “Biosomes”:

And here’s the bottle’s ingredient list for the “Serum”:

Serum Ingredients:
Water (Aqua), Human Bone Marrow Stem Cell Conditioned Media, Cetyl Ethylhexanoate, Niacinamide, Dimethyl Isosorbide, Polyacrylate-13, Glycerin, Hydrolyzed Myrtus Communis Leaf Extract, Butylene Glycol,
Carbomer, Polysorbate 20, Palmitoyl Tripeptide-1, Palmitoyl, Tetrapeptide-7, Polyisobutene, Benzyl Alcohol, Salicylic Acid, Sorbic Acid, Sorbitan Isostearate, Carnosine, Ilex Paraguariensis Leaf Extract, Maltodextrin,
Disodium EDTA, DOTAP, DSPC, DSPE, DSPE PEG, Sodium Chloride, Disodium Phosphate, Potassium Phosphate, Potassium Chloride, Phosphatidylcholine, Phosphatidylserine, Sphingomyelin, Cholesterol, Mannitol,
Trehalose, sh-Oligopeptide-33, sh-Polypeptide-58, sh-Polypeptide-5, sh-Polypeptide-2, sh-Polypeptide-67, sh-Polypeptide-66, sh-Polypeptide-10, sh-Polypeptide-3, sh-Polypeptide-62, sh-Polypeptide-14,
sh-Oligopeptide-2

Bottome line. Private equity is ruining many things and now they’re lying to the public about skin care ingredients.

If you’d like to read about the science of exosomes and liposomes, you can read my 30 page academic book chapter, peer-reviewed, that I published in 2016 with Elsevier, called “Exosomes: smart nanospheres for drug delivery naturally produced by stem cells.“

Mechanisms Of Action of NeoGenesis Hair Thickening Serum

Topical application of Hair Thickening Serum (HTS) promotes hair growth by two key means: Providing, 1. Skin and hair follicle endogenous molecules from skin and hair follicle stem cells (Adipose mesenchymal stem cells, fibroblasts, and dermal papillae) that drive and maintain the transition from telogen to anagen, and 2. Botanical ingredients normally derived from healthy diets that support hair growth.

Simple topical application of NeoGenesis Hair Thickening Serum, b.i.d., twice daily.

Let’s look at the hair growth cycle, and some of the many factors affecting hair growth. I’ll then explain some the mechanisms by which HTS drives the hair follicle to the anagen phase.

Figure 1. Schematic of the hair growth cycle and the factors that may influence a transition from anagen to telogen vs. telogen to anagen phase. From Natarelli et al, 2023.

HTS Mechanisms of Action in the Hair Growth Cycle

HTS’ mechanisms of action at the hair follicle are many. Here I consider a simplified summary of some of the pathways that the stem cell released molecules and botanical ingredients activate or inhibit to drive and maintain the follicle’s transition to the anagen phase.

Transition from Anagen to Telogen

Inflammation – An immunoprivileged state in the follicle is needed to drive anagen, and inflammation transitions the follicle to telogen instead (Bertolini et al, 2020). HTS reduces inflammation in the innate and adaptive immune systems by using the secretome from adipose mesenchymal stem cells – both the exosomal fraction and soluble fractions that act synergistically to optimally reduce inflammation (González-Cubero et al, 2022; Mitchell et al, 2019)

Hormone – ADSC secretome inhibits negative effects of DHT on hair growth (Tang et al, 2023; Fu et al, 2025).

Poor Nutrition – HTS contains nutrients to support hair growth. Larix Europaea Wood Extract, containing Dihydroquercetin-glucoside (polyphenol), EGCG (polyphenol catechin), glycine, zinc, Camellia Sinensis Leaf Extract, Santalum Acuminatum Fruit Extract, Citrus Glauca Fruit Extract, Acacia Victoriae Fruit Extract, Trifolium Pratense (Clover) Flower Extract (providing an abundance of polyphenols and antioxidants).

Stress – ADSC secretome mitigates immunological disturbances affecting the hair follicle (HF) and contributing to hair loss. ADSCs are able to suppress lymphocyte proliferation and, inhibit complement activation and dendritic cell differentiation from monocytes and therefore are considered natural immunosuppressants (Salhab et al, 2022).

Transition from Telogen to Anagen

Blood Flow – Secretome of ADSCs promotes angiogenesis and increased blood flow to follicles (Silveira et al, 2022; Zhu et al, 2020)

Direct stimulation of Hair Growth – Exosomes from dermal papillae cells drive hair follicle stem cell proliferation to rebuild hair follicle (Li et al, 2023), while fibroblasts provide many building-block proteins need to reconstruct the follicle architecture as it transitions from telogen to anagen (Suh et al, 2023).

Increased Local Growth factors – Fibroblasts (Lin et al, 2015), ADSCs (Won et al, 2017), and dermal papillae (HU et al, 2020) secretome all provide necessary growth factors to induce transition to anagen

References

Bertolini M et al (2020) Hair follicle immune privilege and its collapse in alopecia areata. Exp Dermatol. 29: 703–725.

Fu Y, Han YT, Xie JL, Liu RQ, Zhao B, Zhang XL, Zhang J, Zhang J. Mesenchymal stem cell exosomes enhance the development of hair follicle to ameliorate androgenetic alopecia. World J Stem Cells 2025; 17(3): 102088

Fu Y, Han YT, Xie JL, Liu RQ, Zhao B, Zhang XL, Zhang J, Zhang J. Mesenchymal stem cell exosomes enhance the development of hair follicle to ameliorate androgenetic alopecia. World J Stem Cells 2025; 17(3): 102088 [PMID: 40160691 DOI: 10.4252/wjsc.v17.i3.102088]

González-Cubero, E et al (2022) María L. González-Fernández, Elias R. Olivera, Vega Villar-Suárez,Extracellular vesicle and soluble fractions of adipose tissue-derived mesenchymal stem cells secretome induce inflammatory cytokines modulation in an in vitro model of discogenic pain,The Spine Journal,Volume 22, Issue 7,2022, Pages 1222-1234

Li J, Zhao B, Yao S, Dai Y, Zhang X, Yang N, Bao Z, Cai J, Chen Y, Wu X. Dermal PapillaCell-Derived Exosomes Regulate Hair Follicle Stem Cell Proliferation via LEF1. Int J Mol Sci. 2023 Feb 16;24(4):3961.

Lin WH, Xiang LJ, Shi HX, Zhang J, Jiang LP, Cai PT, Lin ZL, Lin BB, Huang Y, Zhang HL, Fu XB, Guo DJ, Li XK, Wang XJ, Xiao J. Fibroblast growth factors stimulate hair growth through β-catenin and Shh expression in C57BL/6 mice. Biomed Res Int. 2015;2015:730139.

Mitchell R et al (2019) Secretome of adipose-derived mesenchymal stem cells promotes skeletal muscle regeneration through synergistic action of extracellular vesicle cargo and soluble proteins. Stem Cell Res Ther. 10(1):116.

Natarelli N, Gahoonia N, Sivamani RK (2023) Integrative and Mechanistic Approach to the Hair Growth Cycle and Hair Loss. J Clin Med. 2023 Jan 23;12(3):893.

Salhab O, Khayat L, Alaaeddine N (2022) Stem cell secretome as a mechanism for restoring hair loss due to stress, particularly alopecia areata: narrative review. J Biomed Sci. 2022 Oct 5;29(1):77.

Shiqi Hu et al. (2020) Dermal exosomes containing miR-218-5p promote hair regeneration by regulating β-catenin signaling.Sci. Adv.6,eaba1685(2020).

Silveira BM, Ribeiro TO, Freitas RS, Carreira ACO, Gonçalves MS, Sogayar M, et al. (2022) Secretome from human adipose-derived mesenchymal stem cells promotes blood vessel formation and pericyte coverage in experimental skin repair. PLoS ONE 17(12): e0277863.

Suh SB, Ahn KJ, Kim EJ, Suh JY, Cho SB. (2023) Proteomic Identification and Quantification of Secretory Proteins in Human Dermal Fibroblast-Conditioned Medium for Wound Repair and Hair Regeneration. Clin Cosmet Investig Dermatol. 2023;16:1145-1157

Tang, Xin, Cao, Cuixiang, Liang, Yunxiao, Han, Le, Tu, Bin, Yu, Miao, Wan, Miaojian, Adipose-Derived Stem Cell Exosomes Antagonize the Inhibitory Effect of Dihydrotestosterone on Hair Follicle Growth by Activating Wnt/β-Catenin Pathway, Stem Cells International, 2023, 5548112, 20 pages, 2023.

Won CH et al (2017) The Basic Mechanism of Hair Growth Stimulation by Adipose-derived Stem Cells and Their Secretory Factors. Curr Stem Cell Res Ther. 2017;12(7):535-543

Zhu, D., Johnson, T.K., Wang, Y. et al. (2020) Macrophage M2 polarization induced by exosomes from adipose-derived stem cells contributes to the exosomal proangiogenic effect on mouse ischemic hindlimb. Stem Cell Res Ther 11, 162.

Why I Formulate With Chondrus Crispus Extract, and Why It’s Not Comedogenic

Chondrus crispus extract is a polysachharide, which are not comedogenic, and is known for its anti-inflammatory, moisturizing, and wound-healing properties on human skin.

NeoGenesis is a biotech company that has the most advanced skin care products on the market, utilizing, for example, our S2RM – stem cell released molecules technology (exosomes, ectosomes, and soluble fraction) that is the most advanced penetration technology in the skin care marketplace. At NeoGenesis we feature science-to-market ingredients that work and are backed by scientific and clinical studies. Chondrus crispus extract is one the science-to-market ingredients used by NeoGenesis. I’ll dig into the science of Chondrus crispus extract (CCE) in the next paragraph, but even a cursory online search of the ingredient gives you an outline of how good this extract is for the skin. Whether it’s SpecialChem, EWG, or Paula’s Choice, scientists reviewing the studies of Chondrus crispus extract all extole its virtues in skin care. Little wonder the ingredient is widely used in skin care products.

The chondrus crispus extract we use at NeoGenesis is a refined polysaccharide that has many benefits and is not comodogenic. Recent studies have found CCE mitigated inflammation and improved scratch-wound healing, and reduce environmental stress. A number of beneficial metabolites can be obtained from algae, including antioxidants, mycosporine-like amino acids, carotenoids, pigments, flavanoids, and polysaccharides. The type of polyssacharide found in chondrus crispus extract has been found to suppress oxidative stress, reduce melanogenesis, and inhibit photodamage. Further, CCE is sustainably sourced unlike a number of competing ingredients.

Iodine is an esential ingredient for skin health. Most multivitamins contain 150 mcg of iodine per daily dose, about 150 ppb. In our Barrier Renewal Cream, we use 10 parts per billion (ppb) of iodine, whcih is an extremely low concentration, representing 10 units of iodine within one billion total units. The use of iodine is being used as an active dermal agent in the treatment of inflammatory, immune-mediated and infectious diseases, e.g. psoriasis, eczema, lupus vulgaris, syphilis. Protection against UVB-induced damage and relief of inflamed skin condition has also been demonstrated (Greenwald et al, 2017).

Further, the thyroid hormone Triiodothyronine (T3) is made in the skin and requires dietary iodine to make this hormone.Control of epidermal cell production and barrier function is depenedent on this pathway (Antonini et al, 2013). Lack of iodine and thyroid hormone cause many skin conditions and loss of hair.

CCE also contains 15 of the 18 essential elements that make up the human body. This includes calcium, sulfur, magnesium, potassium, vitamin A, and vitamin K. Further, because CCE contains sulfur, it may help to reduce sebum production. CCE also contains omega-3 fatty acids, good for the skin, including acneic skin, whether topical or oral.

You can also read what other scientists and physicians say about the benefits CCE when topically applied to the skin in the popular press here, and here.

Why I Don’t Formulate Products with SLS

Despite the years of research on the ill effects of SLS (sodium lauryl sulfate), I continue to hear that people, including dermatologists, are using products with this ingredient, including shampoos.

If you’ve ever Googled the causes of a skin irritation or damaged hair, you’ve likely seen posts about SLS, or sodium lauryl (or laureth) sulfate, a common ingredient in beauty products, cleansers, shampoos, toothpastes, and cleaning products.

So what does this ingredient do, why is it in everything, and what does the evidence say about how safe it is?

When we use a cleanser or shampoo, the product usually contains a detergent. That detergent is called a surfactant. A surfactant allows the oil and water molecules to bind together – it’s what’s found in soaps and detergents so we can wash our oily faces or dishes with water and remove the grime.

Sodium lauryl sulfate (SLS) is a surfactant, and its efficacy, low cost, abundance and simplicity mean it’s used in a variety of cosmetic, dermatological, and consumer products.

Our skin’s outermost layer, the stratum corneum of the epidermis, is specially designed to keep harmful things out, and this is where a surfactant can cause problems. Using chemicals that weaken this barrier defence mechanism can potentially cause our skin harm.

As the outermost layer of the epidermis, the stratum corneum is the first line of defense for the body, serving an essential role as a protective skin barrier against the external environment. The stratum corneum aids in hydration and water retention, which prevents skin cracking, and is made up of corneocytes, which are anucleated keratinocytes that have reached the final stage of keratinocyte differentiation (From Murphrey et al, 2022).

Some surfactants are more irritating to our skin than others. For something to be harmful, irritating or allergenic, it has to fulfill two criteria. It has to have been found in studies to irritate human skin, and it has to have the ability to penetrate the skin. SLS does both. It penetrates the stratum corneum and induces an immune reaction, and degrades the structure of the barrier.

Scientists in Germany tested 1,600 patients for SLS irritancy and found 42% of the patients tested had an irritant reaction. Another study, on seven volunteers over a three and a half month period, found regular contact caused irritation, and the irritation subsided once the skin was no longer exposed to SLS. Another study found the warmer the water used with SLS, the more irritating it will be.

SLS is a well established irritatant and is used as a positive control in dermatological testing. That is, new products being tested to see how irritating they might be to human skin are compared to the known irritant, SLS. If a person is sensitive to SLS, they might find the area that has been in contact is red, dry, scaly, itchy or sore. It’s also important to note there’s no scientific evidence SLS causes cancer, despite what is often posted on the internet. So, it’s probably OK to use SLS in products that are used for household cleaners.

Who should avoid SLS?

Everyone, especially people with a history of sensitive skin, hyperirritable skin and patients suffering from skin conditions such as atopic dermatitis (eczema), rosacea, and psoriasis are best to avoid products containing SLS. If you think it might be SLS causing a skin irritation, stop the use of the product and look for products that don’t contain SLS.

Epithelial Barrier Dysfunction in Noncommunicable and Communicable Diseases

The modern world’s dramatic increase in the number and types of chemicals in which man is exposed, a major part of of someone’s exposome, responsible for about 90% of diseases (not genetics), is causing a dramatic rise in noncommunicable and communicable diseases. Over 350 000 chemicals and mixtures of chemicals have been registered for production and use, up to three times as many as previously estimated, and an underestimate of the true number of chemical types that have been produced and commercialized. As the skin and other epithelial tissues are compromised and exposed to communicable diseases, skin and epithelial transmitted diseases are on the rise. For example, the shingles virus can enter through the skin or the epithelial tissue in our respiratory tract, and having shingles can even lead to increased risk of dementia (2nd Ref). Further, a compromised skin epithelial barrier caused by environmental factors such as mechanical trauma, exposure to exogenous proteases in microorganisms and our food, detergents, and air pollution can activate the innate and adaptive immune systems, inducing keratinocytes to release pro-inflammatory cytokines and chemokines and enhancing the antigen presentation by intradermal Langerhans cells (LCs) and dermal DCs and activating T-cells. In turn, for example, activation of T2 type T-cells leads to IL-4, IL-5, and IL-13 secretion, provoking skin barrier alteration, immune cell infiltration into skin, and itch as observed in atopic dermatitis. 

The first essential step to skin immunity is the epithelial barrier, as infection and resulting inflammation are impossible without first breaching it. Epithelia, coated with a sugary glycocalyx, not only comprise our skin but also the mucosal membranes that line our organs. Their ability to secrete squalene, mucus, lipids, and antimicrobials help protect against pathogen invasion. Additionally, epithelia can prevent inflammation by physically shoving out cells infested with toxins, allergens, antigens, pathogens, or other damage by seamlessly extruding them. This is a strategy employed by not only epithelia, but also our hair does the same as it sheds. Given that chronic inflammation could stem from a defective epithelial barrier, the current approach of treating only the inflammation will only partially mitigate symptoms of a more central problem, ongoing wound healing and disrupted barrier.

Scientists now understand that in patients with allergic disease, regardless of tissue location, the homeostatic balance of the epithelial tissue barrier is skewed toward loss of differentiation, reduced junctional integrity, and impaired innate defense and a hyperactive adaptive (trained immunity) immune system. Importantly, epithelial dysfunction characterized by these traits appears to pre-date a predisposition to immunological responses against a range of antigens or allergens, and development of allergic disease.

From the disease perspective, trained immunity is beneficial, as it improves the host’s defense against subsequent infection from pathogens. However, it can also be detrimental and result in overly active immune responses or chronic inflammation.  Even the innate immune system has some memory, given evidence that components in House Dust Mite extract activate and likely train macrophages to produce high amounts of CCL17, IL-6, and cysteinyl leukotrienes following re-exposure to HDM through the TNF-α and PGE2 pathways. Thus, an activated immune system, one that has memory and is primed to react, can lead to sensitivities that may be triggered by an overabundance of chemicals in the environment, and those sensitivities heightened by a disrupted barrier.

Evidence that epithelial barrier dysfunction explains the growing prevalence and exacerbations of inflammatory diseases such as eczema has grown through many studies performed world-wide. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s that cannot be accounted soley by the emergence of improved diagnostic methods. They are indeed increasing in prevalence, i.e. the number of afflictions per 1,000 people.

Eepithelial barrier dysfunction enables the microbiome’s translocation from the skin’s surface to interepithelial and deeper subepithelial areas, doing in combination with allergens, toxins, pathogens, and pollutants. Thereafter, microbial dysbiosis and possible infection, characterized by colonization of opportunistic pathogenic bacteria and loss of the number and biodiversity of commensal bacteria results. Local inflammation, impaired tissue regeneration, and remodeling characterize the skin that suffers from impaired barrier. For example, commensal bacteria on the skin’s surface are important for epidermal lipid synthesis and improve barrier function. The skin’s microbiome is therefore critical to maintaining epidermal barrier function. The infiltration of inflammatory cells and inflammatory cytokines to affected tissues is part of the immune system’s response to erradicate invading bacteria, allergens, toxins, and pollutants away from the deep tissues. As Peter Elias, M.D. has written, “AD [atopic dermatitis] can be considered a disease of primary barrier failure, characterized by both a defective permeability (Proksch et al., 2006, and references therein) and antimicrobial function.” Further, inflammatory cells and inflammatory cytokines that migrate from the skin to other organs may play roles in the exacerbation of various inflammatory diseases in other organs. Thus, inflammation iniated in the skin may contribute to chronic inflammatory diseases in other tissues.

What Dr. Elias has been saying is that the permeability-barrier abnormality in AD is not merely an epiphenomenon but rather the “driver” of disease activity, an “outside–inside view of disease pathogenesis” (Elias and Feingold, 2001). The evidence for this is: (1) the extent of the permeability-barrier abnormality parallels severity of disease phenotype in AD, (2) both clinically uninvolved skin sites and skin cleared of inflammation for as long as 5 years continue to display significant barrier abnormalities, (3) topical artificial barrier therapy comprises effective ancillary therapy, and (4) specific replacement therapy, which targets the prominent lipid abnormalities that account for the barrier abnormality in AD, not only corrects the permeability-barrier abnormality but also comprises effective anti-inflammatory therapy for AD (Figure 1; Chamlin et al., 2002). Thus, inflammation in AD may begin with insults from without, i.e. the exposome.

That barrier insult can then activate epithelial cells in the skin, keratinocyes, which are non-professional immune cells, but do possess MHC-II molecules, that present antigens to professional immune cells, such as T-cells. Thus, with disrupted barriier, the keratinocytes can recognize antigens and present them to the immune system, leading to inflammation. More and more, scientists are discovering how epithelial cells are part of the immune system, regardless in which organ they exist. Key here is to protect barrier function in all of our epithelial tissues, including the skin.

So if inflammatory diseases such as eczema and psoriasis are environmentally triggered and lead to barrier dysfunction and resultant inflammation, what can we do?

First, calm the inflammation. It’s destructive and further degrades the epidermal barrier. S2RM technology (in NeoGenesis Recovery) is great for reducing inflammation, doing so in both the innate and adaptive immune systems.

Second, use a topical product that provides the 3 lipids and natural moisturizing factors that are needed to rebuild normal stratum corneum and barrier function. One product to use is NeoGenesis Barrier Renewal Cream (BRC).

Third, use a product that provides instantaneous barrier function and commensal bacteria. The instantaneous barrier allows the BRC to rebuld the natural barrier function over time, and the commensal bacteria help to rebuild the barrier through activation of lipid synthesis by skin cells. The commensal bacteria in Neogenesis MB-2 also help to reduce the Staphylococcus aureus infection often assicated with disrupted barrier function.

So remember, these inflammatory skin conditions are triggered by the environment. Therefore, their treatment and prevention means that if you change your environment, you can prevent or treat these diseases. Part of changing your environment is the careful choice of topical products to reduce inflammation and renormalize the structure and function of your skin.