Thinking about trying DefenAge? You may want to read this first. | BareFacedTruth.com

Thinking about trying DefenAge? You may want to read this first.

“Breakthrough” skincare products always arrive with a big marketing splash, often including testimonials from key opinion leaders in dermatology or aesthetic medicine. Even when such august names offer their well-considered opinions, a dash of that proverbial grain of salt might be something to consider as well.

When your BFT hosts started exhibiting at medical trade shows a few years ago, we seldom met a physician who had more than cursory familiarity with the complex cellular language of human cells. The reason is simple: there  are hundreds of individually identified bio-signals and trillions of cells. No wonder most practitioners had little more than passing familiarity with the topic. If we did find someone with in-depth knowledge, they were more than likely PhD level specialists in the field, not practicing physicians.

EXPERTS? MAKE SURE.

After several years of lecturing throughout North America, Europe, the Middle East, and Asia, the majority of practicing physicians still consider the field of topical bio-signals in skincare a black box. And based on numerous conversations through the years, that is true of some of the biggest names in dermatology, anti-aging medicine, plastic surgery and other medical specialties. People with busy practices can only keep up with so much – reading journals and attending specialty academic lectures takes time and effort. As prior busy practicing specialists themselves, your BFT hosts find no fault on that score with anyone.

We have covered the topic in some depth. In the past, BFT has written about the questionable and utterly non-physiologic use of single bio-signals (e.g. EGF), the differences in the secretomes of fat, bone marrow and umbilical cord derived stem cells, PRP (platelet rich plasma), the questionable ethics of using honest-to-goodness human embryonic stem cells to create skincare products without informing consumers of that fact (to wit, the CSC14 cells used to produce ingredients in Provoque come from human embryos), and the (to us) illogical use of lysed fibroblasts (NeoCutis) or lysed “parthenogenic” stem cells (LifeLine) in skincare.

Such lysed cell-derived ingredients seemed non-phsiologic to us then, and still do today. Fibroblasts are puny weaklings when it comes to secreting bio-signals, and there are no parthenogenic stem cells in human physiology, hence no proven role for them in the repair and regeneration of injured (i.e. aging) skin.  That did not stop International Stem Cell Corporation from aggressively marketing LifeLine products, whose breakthrough ingredient is lysed parthenogenic stem cells. Any newly-discovered “breakthrough” ingredient is all it takes to make a compelling marketing message and launch a new product.

Success, however, is not guaranteed. International Stem Cell Corporation still managed to financially implode, even after LifeLine was introduced. BFT reviewed the LifeLine science and company fortunes several years ago.

IF AT FIRST YOU DON’T SUCCEED…

The technology in DefenAge is from the same scientist who was the Director of Research & Therapeutic Development at International Stem Cell Corporation, the developers of LifeLine.

His latest technology, Age-Repair Defensins, is the touted breakthrough ingredient in DefenAge and consists of combined alpha and beta defensins.  The defensins in the product are synthetically produced.

(Just so we’re clear – nothing wrong there. Synthetically produced bio-signals are used in many products, including several we make.)

“INTERESTING” PHYSICIAN TESTIMONIALS about DEFENAGE

 

DefenAge is being marketed aggressively, with much of the collateral in the form of testimonials from KOLs describing clinical results and the scientific foundation of the product, sometimes (in our humble opinion) with questionable use of language.

“The key ingredient, Age-Repair Defensins®, features a stand-alone NATURAL mechanism of action, and has been named “the newest peptide on the market” and “one of the biggest breakthroughs in skin care”. These peptides are synthetically produced and target dormant Skin’s Master Stem Cells.”

“What I thought was so fascinating about DefenAge was that it was something that could simulate dormant stem cells which I had never seen in this type of delivery system before. There are many products claiming to have stem cells, but creams don’t contain living organisms in them so the idea that you could stimulate the skin to become more useful without turning on bad cells was a very exciting proposition.” 

“DefenAge contains peptides. Many people have heard about peptides as they are in a variety of consumer skin care lines. However, there are different types of peptides and the ones that are unique to DefenAgeÒ are called Age-Repair DefensinsÒ. Defensins – a scientific term – are meant to defend the body and there are two kinds of defensins called Alpha and Beta defensins. DefenAge contains both of those defensins which are naturally occurring peptides that work directly to stimulate dormant LGR6 positive stem cells to create enduring new healthy cells from a pool of cells that are themselves young.”

“How is this different than growth factors? Growth factors don’t actually penetrate the skin but they do send signals to turn on cells. The difference is that the cells they (growth factors) are activating are cells that have already been working for the age of the person, so they are turning on tired and fatigued cells, whereas DefenAge’s Age-Repair Defensins act upon the dormant cells that have never been turned on and are basically brand new, never been used before cells – basically very “fresh” cells.”

Age-Repair Defensinsâ[.…]“they awaken key cells that are lying dormant, and are thus younger and healthier, rather than taxing the limited ability of currently active skin cells to affect healthy therapeutic processes.”

 

Huh? What does this even mean? And, where’s your proof ?

The physicians making these statements are all highly respected among their peers, so their comments carry weight and have potential to influence others to adopt the same point of view. Are these esteemed physicians making the takeaway message that “dormant”, as opposed to “fresh” cells, are otherwise doing nothing within the skin until the “Age-Repair DefesinsÒ” show up and awaken them from their slumber?

If so, we say balderdash. Even one of their physician experts appears to think so.

Miami dermatologist, skincare researcher and Founder of Skin Type Solutions, Leslie Baumann, MD, explains, ‘LGR6+ stem cells reside in the hair follicle.  When the skin is wounded, immune cells release defensins which activates LGR6+ to repopulate the epidermis. A new technology using topically delivered defensins has been shown to activate these same LGR6+ stem cells.  This results in rejuvenation of the epidermis through formation of new basal stem cells and new keratinocytes.’

So, it is not necessary to apply topical defensins to activate these LGF6+ cells. They “activate” on a regular basis due to intrinsic signals within the skin. If that were not the case, how would injured skin heal unless DefenAge was slathered onto it? Wouldn’t our cells just remain “dormant?” Someone should inform the other experts.

IS THE PUBLISHED STUDY REALLY WHAT IT CLAIMS? WE DON’T THINK SO.

 

Three oft quoted advocates for DefenAge are physicians who co-authored the debut article about it in the Journal of Drugs in Dermatology. These authors are also co-owners of the company that produces the product. Remember that grain of salt we mentioned above? Two of the five authors of the study are not owners of the company.

The study title is “Multi-Center, Double-Blind, Vehicle-Controlled Clinical Trial of an Alpha and Beta Defensin-Containing Anti-Aging Skin Care Regimen with Clinical, Histopathologic, Immunohistochemical, Photographic, and Ultrasound Evaluation”. It was published in April 2018, Vol. 17, Issue 4.

The title is not only long, we believe it is grossly misleading.

For those who wonder what the term “vehicle-controlled” means, it is the part of the study design that is intended to eliminate the placebo effect. Neither the study staff nor the study subjects knew whether or not the products a subject was using indeed contained alpha and beta defensins. That’s fine, but from what is revealed in the article, there are a number of additional variables that the study title does not mention.

The list of ingredients in the “vehicle” and “active” versions of three products tested (mask, cream, serum) differ by much more than just alpha and beta defensins. If that is the case, one wonders how such declarative conclusions concerning the efficacy of defensins can be made. A true “vehicle-controlled” study would have varied ONLY by whether or not alpha and beta defensins were in the active versions.

Ingredients in the full formula mask, that are not included in the “vehicle” mask include: Carica Papaya (Papaya) Fruit , Papain, Aloe Barbadensis Leaf Juice, Lactobacillus/Pumpkin Ferment Extract, Lactobacillus/Punica Granatum Fruit Ferment Extract, Sea Whip Extract.

Ingredients in the full formula cream, that are not included in the “vehicle” cream include: Niacinamide, Yeast Extract, Phospholipids, Alpha-Defensin 5, Beta-Defensin 3, Hyaluronic Acid, Ophiopogon Japnicus Root Extreact, Hydrolyzed Candida Saitoana Extract, Sea whip Extract, Lycium Chinense Fuit Extract, Vaccinium Angustifollium Fruit Extract, Vaccinium Marcrocarpon Fruit (Cranberry) Fruit Extract, Panthenol, Albumin, Tocopheryl Acetate, Ubiquinone, L-Alany-L-Glutamine, Leuconostoc/Radish Root Ferment Filtrate, SH Oligopeptide-1 (i.e synthetic version of epidermal growth factor.)

Ingredients in the full formula serum, that are not included in the “vehicle” serum include: Niacinamide, Sinorhizobium Meliloti Ferment Filtrate, Phospholipids, Alpha-Defensin 5, Beta-Defensin 3, Palmitoyl Tripeptide-38 (a peptide also known as MatixylTM synthe’6TM which “evens out skin relief and smooths wrinkles”) Sodium Hyaluronate, Arabidopsis Thaliana Extract, Sea Whip Extract, Ergothioneine, SH Oligopeptide-1 (i.e. synthetic version of epidermal growth factor), Tocopheryl Acetate, Ubiquinone, Leuconstoc/Radish Root Ferment Filtrate, Albumin, L-Alanyl-L-Glutamine, Cetyl Hydroxyethylcellulose, Lecithin, Hydroxypropyl Cyclodextrin.

Far from being an apples-to-apples comparison of the same product with and without alpha and beta defensins, the full ingredient products contain numerous additional active ingredients with peer-reviewed proof of efficacy in improving the appearance of aging skin. The products we developed contain many of the same active ingredients.

So, what is it that accounts for the skin changes reported? The defensins, as the study title implies, or the several other active ingredients that can be found in many other high-quality cosmeceuticals? Or maybe it’s all of them.

This is NOT a “vehicle controlled” trial.  If the intention is to prove the benefits of alpha and beta defensins in skincare, this study does no such thing.

LET’S LOOK AT WHAT THE PUBLISHED LITERATURE SAYS

Dynamics of Lgr6+ Progenitor Cells in the Hair Follicle, Sebaceous Gland, and Interfollicular Epidermis. Stem Cell Reports. 2015 Nov 10; 5(5): 843–855.

“We show that these Lgr6+ (leucine-rich repeat-containing G protein-coupled receptor 6) cells constitute long-term self-renewing populations within each compartment in adult skin.”

Lgr6 Marks Stem Cells in the Hair Follicle That Generate All Cell Lineages of the Skin. Science  12 Mar 2010: Vol. 327, Issue 5971, pp. 1385-1389

“Mammalian epidermis consists of three self-renewing compartments: the hair follicle, the sebaceous gland, and the interfollicular epidermis. [….]Prenatal Lgr6+ cells established the hair follicle, sebaceous gland, and interfollicular epidermis. [….] Adult Lgr6+ cells executed long-term wound repair, including the formation of new hair follicles.”

Transplantation of the LGR6+ epithelial stem cell into full-thickness cutaneous wounds results in enhanced healing, nascent hair follicle development, and augmentation of angiogenic analytes. Plast Reconstr Surg. 2014 Mar;133(3):579-90.

“Stimulation of the follicular bulge LGR5+ and LGR6+ stem cells with the gut-derived human alpha defensin 5 results in decreased bacterial presence, enhanced wound healing, and hair growth from tissues devoid of adnexal structures.”

SO, WHAT DO WE LEARN FROM THESE ARTICLES?

 

It is well established that there are skin stem cells located in the hair follicles, sebaceous glands, and between follicles within the epidermis. These cells are required for skin healing to occur throughout life, meaning they are far from “dormant”. They are on duty continuously, ready to respond to appropriate signals. Alpha defensins can be the signal.  Nothing is said about from where these defensins must originate in order to stimulate stem cell activity.

Topical alpha defensins can promote healing when applied to full-thickness cutaneous (skin) wounds. The alpha defensins can be synthetic and created in a laboratory. In our day-to-day lives, however, the defensins that promote healing are secreted from nearby local white cells (PMN – polymorphonuclear neutrophils) that arrive at sites of injury, and incidentally do so at the bidding of the bone marrow stem cells that migrate to the injury to orchestrate the symphony of healing.

ABOUT DEFENSINS

Defensins are of several types, the most common being alpha and beta,  As a general rule, one can consider alpha defensins to be predominant within the gut, and beta defensins as being predominant in and on the skin.

Alpha Defenins

Alpha defensins are gut peptides involved with innate immunity and regulation of microbial balance in the intestine i.e. they make sure “good” bacteria predominate in the intestinal tract. Alpha defensins are also exceptionally strong neutrophil attractors, which is the sine quo non for INFLAMMATION. Their effect is so potent, they are used as inflammatory markers and correlate highly with atherosclerosis, coronary artery disease and even acne.

Since alpha defensins are pro-inflammatory, which is pro-aging by definition, their application to skin seems like a questionable strategy, especially if done on a regular basis. The following quote is particularly compelling in making the case that alpha-defensins are pro-inflammatory.

“Human neutrophil-derived alpha-defensins (HNPs) are proven capable of enhancing phagocytosis  by mouse macrophages. HNP1-3 have been reported to increase the production of tumor necrosis factor (TNF) and IL-1, while decreasing the production of IL-10 by monocytes. Increased levels of proinflammatory factors (e.g., IL-1, TNF, histamine and prostaglandin D2) and suppressed levels of IL-10 at the site of microbial infection are likely to amplify local inflammatory responses.”  

 Some of our readers may recognize tumor necrosis factor (TNF) and interleukin 1 (IL-1) as two of the most pro-inflammatoroy bio-signals in existence. And because interleukin 10 (IL-10) has pronounced anti-inflammatory potency, the sum total effect of alpha-defensins is decidedly pro-inflammatory. That is fine if robust inflammation is needed to heal an acute wound; increased delivery of oxygen and nutrients is beneficial in such circumstances. But what about when used as an anti-aging ingredient in one’s daily skincare regimen? Is chronic smouldering inflammation something to be actively pursued?

Regular BFT readers are well aware that we consider any effort to induce inflammation as an anti-aging strategy to be irrational and counterproductive. Inflammation is aging by definition. Period. As we have written in BFT many times, subclinical inflammation has an edematous component, which can contribute to plumper skin with reduced appearance of fine lines. But, at what price if smouldering inflammation is slowly damaging tissues?

The physiologic role of alpha defensins is to help maintain healthy gut flora.

The following references provide additional evidence as to the pro-inflammatory nature of alpha-defensins. Of particular interest is the association of alph-defensins in acne, making the deliberate use in facial skincare potentially ill-advised.

Alpha-Defensin: link between inflammation and atherosclerosis. Atherosclerosis. 2007 Oct;194(2):452-7

“The deposition of alpha-defensin in the skin is a strong independent predictor of CAD in men. These results suggest a link between neutrophil activation and progression of atherosclerosis and provide a novel approach to assessment of risk factors for CAD (coronary artery disease).” (Note: the article looked at alpha-defensin withint the skin in CAD patients; not from topical application.)

Enteric α-defensins on the verge of intestinal immune tolerance and inflammation. Semin Cell Dev Biol. 2018 Jan 29.

“The gut is the biggest immune organ in the body that encloses commensal microbiota which aids in food digestion. Paneth cells, positioned at the frontline of host-microbiota interphase, can modulate the composition of microbiota. Paneth cells achieve this via the delivery of microbicidal substances, among which enteric α-defensins play the primary role. If microbiota is dysregulated, it can impact the function of the local mucosal immune system.”

Increased alpha-defensin expression is associated with risk of coronary heart disease: a feasible predictive inflammatory biomarker of coronary heart disease in hyperlipidemia patients. Lipids Health Dis. 2016 Jul 18;15:117

“Polymorphonuclear neutrophils play a pivotal role in inflammation and atherogenesis. Human neutrophil peptides (HNPs) or alpha (α)-defensins are cysteine-rich cation polypeptides that are produced and released from activated polymorphonuclear neutrophil granules during septic inflammation and acute coronary vascular disorders. HNPs cause endothelial cell dysfunction during early atherogenesis.”

Expression of human neutrophil proteins in acne vulgaris. J Eur Acad Dermatol Venereol. 2010 Jan;24(1):32-7

“Our current study demonstrates the novel observation that a recently identified antimicrobial peptide, HNP 1-3, is expressed in neutrophils of acne inflammation but not in uninvolved skin of these patients. These results suggest that HNP 1-3 may contribute to the development of inflammatory lesions of acne.”

Beta Defenins

Beta-defensins are an important family of cationic antimicrobial peptides which greatly enhance the resistance of epithelial surfaces, including skin, to microbial colonization. In contrast to alpha defensins, beta defensins are anti-inflammatory

Identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity. Int J Nanomedicine. 2015; 10: 5423–5434.

“hBD3-3 has the ability to be used as a carrier, and suggest a potential approach to effectively treat inflammatory diseases.”

The Effects of Human Beta-Defensins on Skin Cells in vitro. Dermatology. 2017;233(2-3):155-163.

“Beta defensins exert biological effects on skin cells that are potentially beneficial in wound healing.”

Expression of the peptide antibiotics human beta defensin-1 and human beta defensin-2 in normal human skin. J Invest Dermatol. 2001 Jul;117(1):106-11.

“The localization of human beta defensins to the outer layer of the skin is consistent with the hypothesis that human beta defensins play an essential part in cutaneous innate immunity.”

Human β-defensin-3 increases the expression of interleukin-37 through CCR6 in human keratinocytes. J Dermatol Sci. 2015 Jan;77(1):46-53

“Interleukin (IL)-37, a new member of the IL-1 family, is characterized as a fundamental inhibitor of innate immunity: it dampens the production of proinflammatory cytokines, protects against inflammatory and autoimmune diseases, and plays a potent immunosuppressive role in the pathogenesis of psoriasis.”

Defensins: “Simple” antimicrobial peptides or broad-spectrum molecules? Cytokine Growth Factor Rev. 2015 Jun;26(3):361-70.

“While human α-defensins are mostly expressed by neutrophils, β-defensins are secreted by epithelial cells of the skin and mucosae. Besides their anti-microbial activity, accumulating data emerged in the past decade indicating that defensins have extended functions in human physio(patho)logy. Indeed, defensins appeared as modulators of the adaptive immune system and angiogenesis, key mediators of wound healing and determinant players in male fertility.”

Identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity. Int J Nanomedicine. 2015 Aug 26;10:5423-34

Human beta-defensins (hBDs) are crucial factors of intrinsic immunity that function in the immunologic response to a variety of invading enveloped viruses, bacteria, and fungi. hBDs can cause membrane depolarization and cell lysis due to their highly cationic nature. These molecules participate in antimicrobial defenses and the control of adaptive and innate immunity in every mammalian species and are produced by various cell types. [….] Our findings indicate that hBD3-3 may be conjugated with drugs of interest to ensure their proper translocation to sites, such as the cytoplasm or nucleus, as hBD3-3 has the ability to be used as a carrier, and suggest a potential approach to effectively treat inflammatory diseases.

BEWARE: USE OF DEFENAGE WITH MICRONEEDLING CAN BE PROBLEMATIC.

One of the physician testimonials touting DefenAge compared the benefits of PRP (platelet rich plasma) and DefensAge when used in conjunction with microneedling of the face. In the study, PRP was used at time of needling on half of the patients and DefenAge applied 48 hours after treatment on the other half of patients. The reported result was DefenAge patients had superior aesthetic outcomes. Without going into the specifics of that trial, we feel obliged to caution BFT readers to NOT use DefenAge at or near the time of microneedling treatment. Be sure to wait the 48 hours if interested in seeing how, and if, DefenAge can enhance results. The reason for this has to do with the presence of several types of silicone in the ingredient list of DefenAge

The ingredient deck of DefenAge is below. Please note it contains several kinds of silicones (in bold), something proven to be a potential inciting ingredient for granulomatous dermatitis. The enhanced penetration that microneedling creates, can allow such foreign substances to gain entrance into the skin with potential ill effects.

Water (Aqua), Cyclopentasiloxane, Glycerin, Niacinamide, Sinorhizobium Meliloti Ferment Filtrate, Dimethicone, Polysorbate 20, Dimethicone/Vinyl Dimethicone Crosspolymer, Lauryl PEG-9 Polydimethylsiloxyethyl Dimethicone, Ammonium Acryloyldimethyltaurate/ VP Copolymer, Phospholipids, Alpha-Defensin 5, Beta-Defensin 3, Palmitoyl Tripeptide-38, Sodium Hyaluronate, Arabidopsis Thaliana Extract, Sea Whip Extract, Ergothioneine, Helianthus Annuus (Sunflower) Seed Oil, Rosmarinus Offinalis (Rosemary) Leaf Extract, SH Oligopeptide-1, Tocopheryl Acetate, Ubiquinone, Leuconostoc/Radish Root Ferment Filtrate, Albumin, Gelatin, L-Alanyl-L-Glutamine, Caprylic/Capric Triglyceride, Cetyl Hydroxyethylcellulose, Lecithin, Hydroxypropyl Cyclodextrin, Phytic Acid, Phenoxyethanol, Caprylyl Glycol, Ethylhexylglycerin, Hexylene Glycol, Sodium Chloride.

39 Comments

  1. joan says:

    So, would the defenage product be better if it contained beta defensins and eliminated the alpha defensins?

    • drjohn says:

      Yes, absolutely. Although defensins alone may not provide all that is needed for a optimal anti-aging skin care strategy.

  2. Sonya says:

    I love you guys, keep up the good work, I would pay for a subscription to your honesty. It’s hard to find these days!
    Love,
    Sonya Ellis, APRN, CPSN, CANS
    Certified Plastic Surgery and Aesthetic Nurse Practitioner

    • drgeorge says:

      Can’t help it, Sonya. We have to acknowledge and thank you for such a kind compliment. Your BFT hosts, DrJohn and DrGeorge, have spend untold, unpaid hours in this labor of love. Our mission is to educate, inform, and entertain. We’re pleased you feel we are succeeding.

  3. Carmen says:

    Since I have been using this product my cheeks have become red and inflamed is this because of the Alpha Defensins do you think? I have been searching for reveries and the only one I can find are really great about the product and dint mention anyone else having this issue

  4. This is valuable to me, as an esthetician who also performs cosmetic tattoo artistry, mainly for the benefit of scar revision and camouflage.
    It also strengthens my go-to resource for dermal needling, Dr. Lance Setterfield’s cautions about using anything but sterile saline and higher molecular weight hyaluronic acid as potentially inflammatory and therefore, counterproductive.
    Thank you for this research.

  5. Rima says:

    I’m with Sonya. Just 😍 you both, DrG/DrJ

  6. Melinda Stewart says:

    I recently went to an aesthetician for my first Botox treatment on my forehead. I’m 58.
    She said I’ve waited too late and the 11’s are permanently wrinkled. She put me on DefendAge
    Saying after using it for 4-5 months I should be ready for good results with Botox. She said that this product is medicine based and not an over the counter product. I’m skeptical! Any advice?

    • drgeorge says:

      Not sure what “medicine based” means. My presumption is your aesthetician is referring to the company’s literature about how the defensins in the product are “stimulating” otherwise “dormant” stem cells within hair follicles in the skin. Their marketing materials imply these cells are otherwise sitting idly by without a “mission” in life unless DefensAge is slathered on. Read the post about this product again and you will see how we think the marketing message is misleading and inaccurate.

  7. Rimavh says:

    I’ve heard the mask is good but I suspect it’s because of all the other ingredients that will make the skin feel good.
    Can you please tell me about Infusiolife? They claim to also “activate” the bodies growth factors via bone marrow derived (but synthetically produced) bio signaling

    • drjohn says:

      I see no ingredients list (must be a secret). This looks to be a cosmetic spinoff of infusio in Beverly Hills https://www.infusio.org/ https://plus.google.com/106797841926944898518 run by german naturopath Phillipe Battiade. Naturopathy is quackery, not real medicine by real physicians & scientists. We have seen many marketing ploys about stem cell “activators” which is specious logic. Mesenchymal stem cells in our bodies can be compared to a paramedic squad called to the site of emergencies to provide rescue and repair from all sorts of nasties. The easiest way to activate them? Infuse nasties (toxins). Its like homeopathy where a little poison is supposedly good for you. Activators tend to be inflammatory agents. MSC’s come along to put out the fire. So does that make the act of setting your skin on fire a good thing?

  8. joanne says:

    Would the new multi center double blind study published in April in the Journal of Drugs and Dermatology change any of the previous thoughts?
    http://jddonline.com/articles/dermatology/S1545961618P0426X/1

    “Conclusions: A 3-product skin care regimen containing alpha and beta defensins globally improves the visual appearance and structure of aging skin without irritation, dryness, or inflammation.”

    • drgeorge says:

      Not a whit, and for the same reasons we cited in the post on Defenage.

      The study title in the JDD article implies that it the alpha and beta defensins that are responsible for all the improvements documented, yet the experimental design proves nothing of the sort.

      A “vehicle-controlled” trial means that the control product and the test product differ only by the active ingredients being tested, which the study title strongly suggests are the defensins. Re-read the ingredient decks below and note how many additional ingredients are in the study products that are not in the “vehicle”. An excerpt from our post follows:

      The study title is “Multi-Center, Double-Blind, Vehicle-Controlled Clinical Trial of an Alpha and Beta Defensin-Containing Anti-Aging Skin Care Regimen with Clinical, Histopathologic, Immunohistochemical, Photographic, and Ultrasound Evaluation”. It was published in April 2018, Vol. 17, Issue 4.

      The title is not only long, we believe it is grossly misleading.

      For those who wonder what the term “vehicle-controlled” means, it is the part of the study design that is intended to eliminate the placebo effect. Neither the study staff nor the study subjects knew whether or not the products a subject was using indeed contained alpha and beta defensins. That’s fine, but from what is revealed in the article, there are a number of additional variables that the study title does not mention.

      The list of ingredients in the “vehicle” and “active” versions of three products tested (mask, cream, serum) differ by much more than just alpha and beta defensins. If that is the case, one wonders how such declarative conclusions concerning the efficacy of defensins can be made. A true “vehicle-controlled” study would have varied ONLY by whether or not alpha and beta defensins were in the active versions.

      Ingredients in the full formula mask, that are not included in the “vehicle” mask include: Carica Papaya (Papaya) Fruit , Papain, Aloe Barbadensis Leaf Juice, Lactobacillus/Pumpkin Ferment Extract, Lactobacillus/Punica Granatum Fruit Ferment Extract, Sea Whip Extract.

      Ingredients in the full formula cream, that are not included in the “vehicle” cream include: Niacinamide, Yeast Extract, Phospholipids, Alpha-Defensin 5, Beta-Defensin 3, Hyaluronic Acid, Ophiopogon Japnicus Root Extreact, Hydrolyzed Candida Saitoana Extract, Sea whip Extract, Lycium Chinense Fuit Extract, Vaccinium Angustifollium Fruit Extract, Vaccinium Marcrocarpon Fruit (Cranberry) Fruit Extract, Panthenol, Albumin, Tocopheryl Acetate, Ubiquinone, L-Alany-L-Glutamine, Leuconostoc/Radish Root Ferment Filtrate, SH Oligopeptide-1 (i.e synthetic version of epidermal growth factor.)

      Ingredients in the full formula serum, that are not included in the “vehicle” serum include: Niacinamide, Sinorhizobium Meliloti Ferment Filtrate, Phospholipids, Alpha-Defensin 5, Beta-Defensin 3, Palmitoyl Tripeptide-38 (a peptide also known as MatixylTM synthe’6TM which “evens out skin relief and smooths wrinkles”) Sodium Hyaluronate, Arabidopsis Thaliana Extract, Sea Whip Extract, Ergothioneine, SH Oligopeptide-1 (i.e. synthetic version of epidermal growth factor), Tocopheryl Acetate, Ubiquinone, Leuconstoc/Radish Root Ferment Filtrate, Albumin, L-Alanyl-L-Glutamine, Cetyl Hydroxyethylcellulose, Lecithin, Hydroxypropyl Cyclodextrin.

      Far from being an apples-to-apples comparison of the same product with and without alpha and beta defensins, the full ingredient products contain numerous additional active ingredients with peer-reviewed proof of efficacy in improving the appearance of aging skin. The products we developed contain many of the same active ingredients.

      So, what is it that accounts for the skin changes reported? The defensins, as the study title implies, or the several other active ingredients that can be found in many other high-quality cosmeceuticals? Or maybe it’s all of them.

      This is NOT a “vehicle controlled” trial. If the intention is to prove the benefits of alpha and beta defensins in skincare, this study does no such thing.

  9. Lisa OConnor says:

    I have been doing micro needling , more recently with the new radio wave pen and have seen great results. It makes sense that if you stick needles in the skin it will create a cell rejuvenation Im no scientist but it makes sense and seems to work

    • drjohn says:

      Hi Lisa. The trick with microneedling is to cause healing, but to shut down inflammation as soon as possible so that the healing that happens does so in an non-inflammatory tissue environment. If you do so you will heal like a very young person, with a great aesthetic result. If on the other hand you add to inflammation, or if it just persists because you are of a certain age (like myself) you tend to heal with fibrosis, which can cause problems and leads to an older, not younger appearance. So what you put on your face before, during, and/or after microneedling makes a big difference, no matter what the pen type.

  10. Allison C says:

    Thank you for your review of the science involved in these products. I was sent the 3 products for review in my beauty blog. To be honest, I haven’t read about what makes these products different. I had never heard of defensins. I have been using the trio of products for about 7 weeks, and from a product esthetics standpoint, they are very pleasant to use. My skin is nicely hydrated, and I really enjoy using them. Clearly, the hands of time have not been reversed, but my skin looks good and feels healthy. I am having a dilemma – should I review these products that I’ve been enjoying, or should I pass? I don’t want to promote skincare based on faulty science.

    • drgeorge says:

      The decision to review is yours. If you are enjoying the products, say so – you mention your skin “looks good and feels healthy” and is “nicely hydrated”. Your readers deserve your honest opinion.

      Our issue with this product has to with the marketing message being promulgated as well as the prudence of inclusion into the formula of a pro-inflammatory substance knowing it will be applied to the skin on a daily basis.

      Our post mentioned that the article published about the DefenAGE products in the Journal of Drugs in Dermatology carried a misleading title that implied the inclusion of alpha and beta defensins was what lead to the skin improvements described in the study. Nowhere was it mentioned that there were a great number of other ingredients in the products that were NOT in the vehicle products, against which the DefenAGE products were compared. The design of the study cannot therefore prove that alpha and beta defensins were responsible for the improvements observed, yet this is what the title and marketing implies.

      We have no issue with inclusion of beta defensin in the product since that is a normally occurring skin defensin that has proven anti-inflammatory benefit. Alpha defensins, on the other hand, do not naturally occur in the skin UNLESS there is a wound in which case white blood cells that arrive on site to participate in the healing process secrete alpha defensin, which in turn stimulates the LGR6 stem cells found within hair follicles. The marketing messages we have seen seem to imply that these stem cells remain “dormant” indefinitely, and that DefenAGE, and only DefenAGE, will stimulate them. Not true.

      Some interesting references:

      Pro-inflammatory and pro-apoptotic properties of Human Defensin 5 Biochemical and Biophysical Research Communications
      Volume 436, Issue 3, 5 July 2013, Pages 557-562

      Lgr6 Marks Stem Cells in the Hair Follicle That Generate All Cell Lineages of the Skin
      Science Vol 327, Issue 5971, 12 March 2010

      Stimulation of the follicular bulge LGR5+ and LGR6+ stem cells with the gut-derived human alpha defensin 5 results in decreased bacterial presence, enhanced wound healing, and hair growth from tissues devoid of adnexal structures.
      Plast Reconstr Surg. 2013 Nov;132(5):1159-71.

      Alpha-Defensin: link between inflammation and atherosclerosis Atherosclerosis. 2007 Oct;194(2):452-7.

      Alpha-Defensin 5 Expression is Regulated by microRNAs in the Caco-2 Intestinal Epithelial Cell Line.
      J Inflamm Bowel Dis Disord. 2016 Apr;1(1).
      Alpha-defensin DEFA1A3 gene copy number elevation in Danish Crohn’s disease patients. Dig Dis Sci. 2011 Dec;56(12):3517-24.
      Functional intersection of Human Defensin 5 with the TNF receptor pathway. FEBS Lett. 2014 May 21;588(10):1906-12. (Note:TNF is a highly pro-inflammatory cytokine mediated pathway)

  11. Ellen says:

    I have a patient who came in yesterday with the above produce (Defenage) asking my opinion, She purchased them from her dermatologist. How can I communicate to her in a layman’s terms, the information above?

    • drgeorge says:

      As best we can, we try to provide information in a way that is accessible by people of all levels of education on the topic being discussed. Perhaps you can steer this patient to the BFT post and then answer questions after that. If you like, you can forward her questions to us and we’ll handle privately.

  12. Clarissa Hale says:

    Very informative I was thinking about buying defenage… So which product do you own/sell? Or recommend?

    • drgeorge says:

      Just so it’s clear, we strive first and foremost to educate our readers so that they can make informed decisions on their own. That said, we produce our own brands, AnteAGE and AnteAGE MD, as well as have private label relationships with other brands, for whom we manufacture products using our advanced science concepts and technology. Bone marrow derived mesenchymal stem cells are cultured using proprietary techniques in our own laboratory, after which they are filtered out of the nutrient broth and discarded. Within the nutrient broth in which they grow are found many, many molecular bio-signals (cytokines and growth factors) that are identical molecules to those produced by these very special cells within the body of every human alive. Because these cells are the “command and control” of healing of all injuries in all tissues from birth until death, they are perfect within a topical intended to rejuvenate and help heal skin injuries. Because skin ages as the result of the accumulated injuries of the decades one has lived, our products are wonderful anti-aging products, both reparative and preventative. Accelerated healing following CO2 fractional laser (up to 40% less downtime) and visible reductions in inflammation of intact skin, or skin that has had an aesthetic procedure, confirms their benefit. Go to AnteAGE.com to learn more.

  13. Fran says:

    Not sure if you are recommending this product- Radical Anti-Aging System by DefenAGE skincare. I’m looking for a Glow on the face without using so much makeup at age 67!

    • drgeorge says:

      We’re not saying DefenAGE is a bad product; we actually have several ingredients in our AnteAGE and AnteAGE MD brands that are the same. Our criticism comes from the fact that the DefenAGE marketing message is misleading. Their message is that without topical alpha defensins, the stem cells within the follicle that produce new skin cells will sit there dormant doing nothing, which is not true. Our healing physiology mandates that these cells participate in healing throughout life, topical alpha defensins notwithstanding.

      BFT readers know we are not keen on intentionally inflaming the skin – alpha defensins are pro-inflammatory. Beta defensins are a different story; they are part of the natural skin defense against pathological invaders. We are great fans of the bone marrow stem cell secretome, the mix of cytokines and growth factors they produce are pro-healing and anti-inflammatory. That’s why we selected them as the basic technology behind our products. If you want your 67 years old skin to look its best, we don’t think DefenAGE is your best choice. (Pssst – have you tried AnteAGE / AnteAGE MD?)

  14. Kate says:

    Hello, I have been looking into the Defenage skincare line recently and happened upon your review. You bring up a lot of good points that are potentially troubling regarding the efficacy of the skincare line and it’s clinical backing. However, there is one question troubling me. This is the alpha defensin’s link to inflammation. I’m not questioning that. You point out through various studies that it is the HNPs1-3 (derived from alpha defensins) that increase levels of proinflammatory factors (IL-1,TNF,histamine and prostaglandin D2) and suppresses levels of IL-10. You also point out, from a separate article, that HNP1-3 is expressed in neutrophils of acne inflammation. This makes sense in light of the first conclusion about pro inflammatory responses. But, the alpha defensin used in Defenage is Alpha-defensin-5 (DEFA5). Further, it is the alpha defensins 1 and 3 ( DEFA1 and DEFA 3) that code for HNP1-3, not DEFA5. If it is the HNP1-3 that helps spur a proinflammatory response and DEFA5 doesn’t even code for any HNPs than what’s the link between DEFA5 and inflammation. Looking further, I even found an article that stated DEFA5, and DEFA6, are more closely related to beta-defensins (which you state have anti inflammatory properties) then HNPs1-4. What are your thoughts on that? Am I missing something here besides the obvious limitations of the study that was published about Defenage in the journal of drugs and dermatology and the inaccurate statement that the Lgr6 cells are “dormant” etc…? Finally, I apologize for any typos as this comment was composed on my smartphone.

    • drjohn says:

      Great question, Kate. Human Neutrophil Peptides 1-2 (HNP-1-3) are themselves alpha defensins, and their induction is not an obligate step for an alpha (DEFA-1-5) defensin to produce an inflammatory reaction. HNP’s are also not always measured. All alpha defensins are neutrophil attractors and are considered to be inflammatory. Neutrophils themselves are biosignal amplifiers, leading to more alpha defensins.

      DEFA-5 is now recognized as a highly discriminative biomarker for Crohn’s colitis, a very nasty inflammatory bowel disease. Take a look at this publication from 2017: Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease. “Aberrant expression of Human α-Defensin-5 levels using transcript, Western blot, and immunohistochemistry staining levels was significantly upregulated in Crohn’s colitis, p< 0.0001....Among the up-regulated genes were α-defensin-5, other antimicrobial peptides, and mucins" Take note of Table 2. Full list of targets from NanoString Human Inflammation PCR array. It is noted in the text and is well known that the Nanostring array is only measuring inflammatory proteins. Note that all but 2 of the expressed inflammatopry markers go down in this study. HBD-5 goes up 31 fold. Thats a huge amount.

      Here is another interesting new paper. Defens-IN! Human α-Defensin 5 Acts as an Unwitting Double Agent to Promote Shigella Infection.

      Much is not known. I guess the bottom line for me is this – in clinical skin care, with so many great possibilities that are not at all controversial, why choose a biomolecule whose entire function has to do with the gut (especially paneth cells) and is a well know culprit in the inflammatory cascade of major disorders. It suggest something other than diligent scientific logic driving this product formulation.

    • drjohn says:

      Kate, also note what other scientists have published about HD-5
      Pro-inflammatory and pro-apoptotic properties of Human Defensin 5
      Highlights
      • Human Defensin 5 increases pro-inflammatory and cell survival gene expression.
      • Human Defensin 5 signaling is NF-kB-dependent.
      • Human Defensin 5 induces secretion of pro-inflammatory cytokines.
      • Human Defensin 5 induces pro-apoptotic events.

      Predominantly based on the ability of defensins to act as chemoattractants, it was concluded that α-defensins may share a common receptor, distinct from β-defensins [9], [10].

  15. Hi there,

    I am a new reader and came across this site when googling to replace my Defenage. I have been using it for several years with no problem, but you seem to have very definite thoughts against it.

    I am 67, have derma rolled for more years than I can remember. I use a lot of Skinceuticals products. (CE Ferulic, Resveratol BE and HA Intensifier). Why do you recommend to replace the Defenage in my routine?

    • drjohn says:

      Hi Karen. Thanks for your thoughtful comment. I want to reiterate that our mission here is to teach about anti-aging and aesthetic/dermatology science, not to to directly recommend products. If we influence product choices by informing & educating consumers about the (complex yet fascinating) underlying science … well that is consistent with our mission. But we recognize that science is not the only determinant that people use in selecting their skin care routine. There may be aspects of skin care products that have little to do with science. Things like look & feel & smell. Things like convenience (some only available from doctors, some at Walmart), cost (big differences) and even packaging. Some products are expensive enough to be “status symbols”. If you have had experience with a product and find that it works for you, is effective, causes no problems, that experience counts for something as well. With all that in mind, you need to decide what is important to you. I encourage you to look at the science (much is already written here in this BFT thread about defensins as skin care active ingredients) and see what makes sense to you.

      As an avid dermaroller, I would also encourage you to read up on that aspect. In addition to BFT there is Dr. Setterfield’s new book on the subject if you really want to take a deep dive. Written for professionals, but I’m betting you are an advanced user who would be able to gain usable knowledge. Dr. Setterfield and we have embarked on some new lab and clinical studies in microneedling, which we hopefully can report in the near future. The next note I write after this one is to the German engineer who invented the dermaroller about 30 years ago and got this whole movement “rolling”. Sorry, couldn’t help myself.

      Our lab has also developed skin models that allow us to test all manner of ideas in the lab while measuring various biomarkers of cell age and senescence, stress response to chemicals and environment, and to evaluate treatments. This is a whole new arena – senescence, senolytics, senomorphics – and provides new insights into skin cell biology, biochemistry, and regeneration. An hypothesis that we have been nurturing for years involves key differences between wound healing (a survival mechanism) and non-stressed regeneration such as the scar free version of a fetus or the goal of non-fibrotic, scar free, good vs bad collagen, good vs bad elastin “healing” (not the right term if there is no wound but only degenerative changes from aging). A rapidly growing body of medical literature in the anti-aging field is adding weight to our argument.

      The thing about alpha defensins is that they are part of our primitive defenses against infection. In the intestine where the microbiome is diverse and where pathogens pass through regularly (which is where alpha defensins predominate) having a vigorous inflammatory response is a good thing (unless you have Crohn’s where it may become a very bad thing). Alpha defensins are attractants for neutrophils, which is the very definition of inflammatory. But on skin to foster scar-free regeneration? Makes no sense to us. And keep in mind the whole rationale in the first place was based on studies (by our colleague Denver Lough) showing the role of these played in healing troublesome wounds. Where inflammation is required to kick off the sequence. The other part of the hypothesis is that using skin care products with inflammatory ingredients does give results. There is stimulation of fibroblasts (defensively, under these conditions) which then do make more collagen, but it is not the good kind, the basket weave kind. Collagen produced under conditions of inflammation tends to become fibrotic stiff, cord like, hard to remodel. Our fear is that daily application creates a condition of chronic low grade inflammation called inflamm’aging (or skinflamm’aging) which eventually becomes manifest in signs of accelerated aging. It’ still just an hypothesis (we are just starting to test) but we believe that it is the best explanation that brings together the evidence into a unifying explanation. A theory of all things skin.

  16. Wow! Thank you! I love this site. I am an avid skincare fan. I was a tanner many years ago, but I have taken good care of my skin and it shows. I will definitely read Dr. Setterfield’s book. Thank you for the recommendation.

    When I was 53 it was serendipitous that an anti-aging spa opened in the building where I had my business. At first I was not interested in their services, but of course, I got hooked. (In a good way.) The doctor was a fantastic product guru, bringing products from Europe and leading the way through a myriad of skincare products. She introduced me to the derma roller and Environ products about 10 years ago. However she has become a Skincueticals exclusive reseller and I miss learning about what else is out there.

    I definitely do not want accelerated aging! But I wonder if I should introduce something else into my routine to replace it?

    I look forward to following this site and and your research. Thank you Dr John!

  17. Cathy Carey says:

    Morning. I am a nurse and still find the science (and language) quite intimidating here. I try to read these responses and pull out pertinent (and understandable) comments I might find useful but still have a hard time. I turned 60 this year (hardest birthday to date for some reason) and looked in the mirror and suddenly saw an old person. So, off I go to the closest medi-spa (Rejuve) only to find out the marionette lines and my starting to sag jowls/neck need thousands of dollars of care. First, a 7 product skin care regimen for 2 weeks, followed by 2 Halo treatments, then a little bit of filler at the cheek to lift and Botox. Then she said we would consider a vampire facial. Oh boy, not sure this is doable (you know, champagne taste, beer budget). I was able to decrease the number of products I purchased that day to 3, a green tea facial wash, the 8-in-1 BioSerum by DefenAge and a moisturizer with SPF. The list of ingredients on the serum led me to investigate them which is how I ended up here. I was surprised to learn that Sinorhizobium Meliloti is actually a gram-negative bacteria which of course freaked me out (nurse thinking e-coli). So, considering I eat organically, avoid GMO products, exercise daily (outside if possible, yikes) don’t drink or smoke and try to remain optimistic for emotional health; it seems a contradiction to add products to my skin that are chemical based and possibly inflammatory. I should have taken better care of my skin and although I don’t want to apply chemicals to my skin I still walked out of there with $266 worth of products that might be questionable. I guess I should get to the question. Are there any products worth considering that are organic based and chemical free?

    • drjohn says:

      Hi Cathy, you bring up a number interesting points. I’m all in favor of stopping the madness of applying inflammatory ingredients to skin. Since inflammation is the final common pathway leading to tissue aging, it makes no sense. More on that later. Now you do bring up that word “organic”. You may recall from your textbooks that the term describes things that pertain to plants and animals. But it’s meaning has been somewhat distorted in the marketplace, as has the term “natural”. I like to ask the question “what could be more natural (and even organic) to humans than human molecules?” Now that of course begs the question since there are many things that come from humans that are contrary to the premise we just stated – inflammation is bad, anti-inflammation is good. Which is how this thread got started – why apply an inflammatory molecule to skin (even if it is natural, organic, and native human). Especially when you have other biosignaling molecules in the same class that are anti-inflammatory. Nonetheless, I would argue, we are beginning to discover that replacing or amplifying the good (not the evil) humors is a powerful way to moderate aging itself. So, to the extent that we in the past thought that plants had all the answers and were more natural, the new thinking presupposes that there is huge value to understanding how our bodies do things naturally, then try to replicate that. Stem cells (our natural repair and regeneration system), cytokines (the chemicals cells use to communicate), offer great insights. A whole new generation of skin care products is coming to the foreground. Now, chemical free is a tough one. Products you put on your skin are typically emulsions, requiring surfactants to become stable. They contain chemical preservatives so that bugs (like those nasty gram negs you mention) don’t take over while they sit in your bathroom. Most of them have been tested exhaustively and are safe. I would worry less about those than I would about the irrational “active ingredients” we encounter. My advice is to find a purveyor of innovative skin products with ingredients that your level of scientific sophistication tells you makes sense.

  18. Ta Ka says:

    I feel like I finally found a skincare line (defenage) that works on my skin. I secretly hope it will take away my milia one day but for now I’m happy with my skin just looking smoother and more hydrated. I’ve sifted through all of your thoughts and I’m still not sure what to believe. My biggest concern is that I have multiple sclerosis and I’m doing everything I can to avoid inflammation. Are you suggesting that definition could potentially make my autoimmune disease worse?

    • drgeorge says:

      We can see no way in which applying this product to your facial skin is going to in any way exacerbate or affect your autoimmune disorder. It appears from you question that you may not understand what our issue with this product is. It really boils down to the “story” being told by the company.

      Defensins are part of our natural physiology but they have inherent properties, particularly when it comes to calming or inciting an inflammatory response. There are lots of defenses. Their product, and our comments about it, pertain to the specific ones they claim are in the DefenAGE product – a particular alpha and a particular beta defensin.

      Alpha defenses are typically found within the gut and have a pro-inflammatory effect. The claim by the company is that when alpha defensin is applied to the skin, they “awaken” an otherwise dormant population of stem cells found within hair follicles, implying that if you don’t use their product, these cells will stay dormant. That is simply not true. The skin does not normally have alpha defenses produced locally, it does, however, have beta defenses, which are known to be anti-inflammatory.

      One thing the company fails to tell its customers is that alpha defensins are released locally within the skin by a type of white blood cell that always shows up whenever there is any type of injury. It’s presence is an integral part of the inflammatory response, which, as you know, occurs with any type of injury no matter how small or insignificant. Otherwise, no injury would ever heal if alpha defensin is necessary to stimulate the “dormant” stem cells in the skin, and DefenAGE is the only way to get it.

      Their purported science falls apart on that basis alone, but the marketing message gets propagated, nonetheless. As scientists, we are underwhelmed by that product. If you are happy with the results you are getting, it can be related to other ingredients in the product as well. Just imagine all the wonderful facial skin in the world of people who have never heard of DefenAGE. Please be aware that removing milia and hydrating the skin can be accomplished by all sorts of everyday, inexpensive products – you’ll save a bundle.

  19. drgeorge says:

    I am glad to hear that using Defenage will not affect any autoimmune disease, but you seem to be saying that using the product will eventually make one’s skin age faster? Am I misreading your message?

    • drgeorge says:

      We are crusaders against any product with active ingredients that are likely to promote chronic inflammation, something well recognized as pro-aging, not just in the skin but in all tissues.

      DefenAGE boasts that one of it’s “hero” ingredients is an alpha defensin capable of “awakening” slumbering “dormant” stem cells within the hair follicle. The implied response their marketing team seeks is “gee, if I use DefenAGE my stem cells will get busy doing repair work on my skin.” What none of their marketing tells you is that alpha defensins are present in all wounded skin. One particular type of inflammatory cell that migrate to skin injuries secretes alpha defensin, which stimulates the follicular stem cells – no DefenAGE necessary.

      That said, there are other ingredients in their product that can be beneficial. The same ingredients are found in lots of products.

  20. Amy says:

    Please suggest some product lines that you do recommend! I am not savvy enough to sort through all the science, but I do want to take care of my 53 year old skin as best as possible. I have spent too much money and feel at the mercy of the influence of sleek marketing campaigns or dermatologists selling their own brands.

    • drgeorge says:

      Amy, your BFT hosts have many years of experience in the skincare field. We’ve seen (and commented) on the good, the bad, and the outright ugly of the “Wild West” marketplace of skincare. We know how confusing it is for the non-scientist. That said, the best recommendation we can make is to give the AnteAGE and AnteAGE MD brands of products a try.

      As readers know, these are products developed and marketed by DrJohn and DrGeorge when we wear our daytime hats. We believe our scientific foundation most closely mimics how Mother Nature deals with injury, inflammation, and healing. AnteAGE is available online, AnteAGE MD from physician practices. (Contact us privately if you want to know the name of a MD reseller near you.)

  21. Shalini says:

    I was on the verge of purchasing Defenage and stumbled upon your website when doing my research. I reached out to the scientists at Defenage about the alpha-defensins being pro-inflammatory. I received the below response from them. Would love to learn your thoughts.

    Paraphrasing: Alpha defensins are anti-microbial peptides that our bodies produce to fight bacteria. When any inflammation/trauma happens – our immune system immediately increases production of defensins in the area of inflammation TO FIGHT against potential contamination from bacteria…but ironically, for people who are not experts in biology of defensins and even doctors – this look like the defensins cause inflammation because their level is increased in the area of inflammation. Although, again, the increase of the level of defensive in the inflammation is a natural reaction of our bodies to prevent bacterial infection.

    In addition, DefenAge formulas, including “super concentrated” solution of defensins were tested in comprehensive clinical trials that shows that treatment does not causes any inflammation – this fact was confirmed by several methods including histo-pathology of skin biopsies. One of the published studies can be reviewed in Journal in Drugs in Dermatology. Overall, DefenAge was tested and proven in 14 clinical studies.

    • drgeorge says:

      The response from the scientists at Defenage reminds BFT of the age-old question: “Which came first, the chicken or the egg?”

      Defenage is claiming that inflammation causes the secretion of alpha-defensin-5 (the isoform in their product) instead of the other way around. The published literature cited below contradicts their opinion. We stand by ours.

      Consider the following from two published articles focused on alpha defensin-5 :

      “We find that HD-5 induces secretion of IL-8 by epithelial cells in a structure-dependent manner. Furthermore, HD-5 and TNF-a act synergistically to induce secretion.”
      (BFT note: IL-8 and TNF- are highly potent pro-inflammatory bio-signals.)

      Structure-dependent functional properties of human (alpha) defensin 5
      FEBS Letters 581 (2007) 515–520

      “Here, we report on the pro-inflammatory and apoptotic properties of Human Defensin 5, the major antimicrobial peptide of ileal Paneth cells. We find that HD-5 up-regulates expression of genes involved in cell survival and inflammation in a NF-kB-dependent fashion in epithelial cells.”

      Pro-inflammatory and pro-apoptotic properties of Human (alpha) Defensin 5
      Biochemical and Biophysical Research Communications 436 (2013) 557–562

      BFT also finds it interesting that the study published in the Journal of Drugs in Dermatology is once again cited as confirmation that the defensins in Defenage are solely responsible for the skin changes observed. Please re-read our original post on Defenage in which we conclude that the title of the study is utterly misleading.

      The study was not “vehicle controlled” at all. Look at the list of ingredients in the Defenage “test” product and in the “vehicle” product, against which it was tested. For a valid “vehicle controlled” study, the two test formulations MUST be identical except for the alpha and beta defensins. If that is not the case, the title and structure of the study are internally inconsistent; the conclusion and results therefore fatally flawed. As to the other 13 studies you mentioned, please ask Defenage them to provide them. Perhaps they will change our opinion. If they do, we will do a new post and include the data that opened our eyes.

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