Hyaluronic Acid – Yes, Size Does Matter! | BareFacedTruth.com

Hyaluronic Acid – Yes, Size Does Matter!

Being touted by some as a “better” hyaluronic acid (HA) for skin application, low molecular weight  hyaluronic acid (LMW-HA) is in fact a potent stimulus for inflammation and scarring.

We at BFT have found a major disconnect between what the cosmetic industry says is true, and what actual scientists say is true.  So here we go again. We find a number of products claiming to contain a new, improved form of HA that is “low molecular weight”.  As is typical we can trace this myth making back to the ingredient manufacturers, who of course provide “proof”. But, in keeping with  their usual habit, do the wrong experiments and then misinterpret the results to put a positive spin on the matter.
Hyaluronic acid (HA) is ubiquitous in mammals, forming a key component of connective tissue in our bodies.The average person has roughly 15 grams of HA in the body, one-third of which is turned over (degraded and re-synthesized) every day. HA is an important structural molecule in the extracellular matrix of our skin. It is synthesized there by fibroblasts, fibrocytes, and by roving stem repair cells derived from bone marrow(MSC’s)  that show up in case of wounding and other forms of damage.

HA is used therapeutically – it is the stuff of facial fillers, and can be applied topically as a humectant. Being a very large molecule it does not penetrate and instead sits of the skin surface where it binds to water to maintain hydration, and cross links with other HA molecules to knit together a temporary barrier.  Very useful to help maintain skin’s barrier function after minor injuries.  Because our bodies make it – it is completely natural to humans – and therefore very unlikely to cause an allergic reaction.

Diagram showing injury – HA fragmentation into LMW varieties – cytokine induction – inflammation cascade leading to fibrosis and scarring

When wounding or damage (e.g. sunburn) occurs,  there is released early a set of hyaluronidase enzymes, which breaks HAdown into fragments. The size of these can vary from low(LMW-HA) to medium (MMW-HA) molecular weights. HMW-HA has been shown to attenuate the inflammatory response, suggesting that HMW-HA promotes regenerative healing in adult wounds.  On the other hand, LMW-HA and intermediate-weight HA increase the expression of macrophage inflammatory protein-1a and monocyte chemotactic protein-1, which may suggest that LMW-HA is important in the induction of the inflammatory cascade. Other scientific peer-reviewed publications peg LMW-HA as pro-inflammatory by multiple mechanisms: they stimulate macrophages to produce inflammatory chemokines, induce interferons, recruit T-cells, induce IL-12 cytokines, and induce nitric-oxide synthase to produce excess NO2.

In both adults and fetuses, HA levels increase in response to wounding. However, unlike adults, fetuses produce much more HMW-HA in response to injury.  HAS-1 over-expression promotes dermal regeneration in part by decreasing the inflammatory response and by recapitulation of fetal ECM HMW-HA content. (Part of our work involves altering the growth factor and cytokine to more closely resemble a fetal pattern).

The type of collagen produced by to regenerate skin is affected by the relative presence of HMW vs LMW HA. A fine reticular pattern is produced in the non0inflammatory environment of HMS-HA, whereas a more disorganized pattern is seen when HA fragments abound.  The results (scar free vs scarring) has aesthetic implications.

It is of considerable interest that organic “contact sensitizers”  induce production of reactive oxygen species (ROS) and a concomitant breakdown of the extracellular matrix (ECM) component hyaluronic acid (HA) to pro-inflammatory low molecular weight fragments in the skin. So, in some ways, adding LMW-HA topically may replicate that cascade of events.  This makes it especially problematic when you consider the application of HA when the skin barrier has been disrupted, e.g. during microneedling.

Small fragments of the extracellular matrix component hyaluronic acid (sHA) are typically produced at sites of inflammation and tissue injury and have been shown to be associated with tumor invasiveness and metastasis. Exposure of human melanoma cells to small HA fragments leads to nuclear factor kB (NFk-B) activation followed by enhanced expression of matrix metalloprotease (MMP) 2 and interleukin (IL)-8, factors that can contribute to melanoma progression.  This suggests that LMW-HA in melanoma might promote tumor invasiveness by inducing MMP- and cytokine-expression.

According to another study, low molecular weight HA may also play a role in breast cancer metastasis.

There is abundant experimental evidence from the human physiology and biochemistry literature to support the basic notion that LMW-HA is inflammatory, pro-fibrotic, and associated with adult scarring phenotypes rather than fetus-like, scar-free, truly regenerative healing.  The latter is what we want in an any aesthetic procedure, or topical adjunct to a procedure, or just for topical use.

We strongly suggest you review any hyaluronic acid products you may use on yourself or others. Make sure the formulator didn’t fall prey to marketing materials from one of those too-clever-by-half ingredients manufacturers who make up a good story but haven’t a clue about the real science. Caveat emptor!

 

References

  • Jiang D1, Liang J, Noble PW. Hyaluronan as an immune regulator in human diseases. Physiol Rev. 2011 Jan;91(1):221-64. PMID: 21248167.

  • Zgheib C1, Xu J1, Liechty KW1. Targeting Inflammatory Cytokines and Extracellular Matrix Composition to Promote Wound Regeneration. Adv Wound Care (New Rochelle). 2014 Apr 1;3(4):344-355. PMID: 24757589.

  • Voelcker V1, Gebhardt C, Averbeck M, Saalbach A, Wolf V, Weih F, Sleeman J, Anderegg U, Simon J. Hyaluronan fragments induce cytokine and metalloprotease upregulation in human melanoma cells in part by signalling via TLR4. Exp Dermatol. 2008 Feb;17(2):100-7. PMID: 18031543.

  • Esser PR1, Wölfle U, Dürr C, von Loewenich FD, Schempp CM, Freudenberg MA, Jakob T, Martin SF. Contact sensitizers induce skin inflammation via ROS production and hyaluronic acid degradation. PLoS One. 2012;7(7):e41340. PMID: 22848468.

  • Black KE1, Collins SL, Hagan RS, Hamblin MJ, Chan-Li Y, Hallowell RW, Powell JD, Horton MR. Hyaluronan fragments induce IFNβ via a novel TLR4-TRIF-TBK1-IRF3-dependent pathway. J Inflamm (Lond). 2013 May 30;10(1):23. PMID: 23721397.

  • Horton MR1, McKee CM, Bao C, Liao F, Farber JM, Hodge-DuFour J, Puré E, Oliver BL, Wright TM, Noble PW. Hyaluronan fragments synergize with interferon-gamma to induce the C-X-C chemokines mig and interferon-inducible protein-10 in mouse macrophages. J Biol Chem. 1998 Dec 25;273(52):35088-94. PMID: 9857043.

  • Hodge-Dufour J1, Noble PW, Horton MR, Bao C, Wysoka M, Burdick MD, Strieter RM, Trinchieri G, Puré E. Induction of IL-12 and chemokines by hyaluronan requires adhesion-dependent priming of resident but not elicited macrophages. J Immunol. 1997 Sep 1;159(5):2492-500. PMID: 9278343.

  • McKee CM1, Lowenstein CJ, Horton MR, Wu J, Bao C, Chin BY, Choi AM, Noble PW. Hyaluronan fragments induce nitric-oxide synthase in murine macrophages through a nuclear factor kappaB-dependent mechanism. J Biol Chem. 1997 Mar 21;272(12):8013-8. PMID: 9065473.

  • McKee CM1, Penno MB, Cowman M, Burdick MD, Strieter RM, Bao C, Noble PW. Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages. The role of HA size and CD44. J Clin Invest. 1996 Nov 15;98(10):2403-13. PMID: 8941660.

  • Ghosh S1, Hoselton SA2, Wanjara SB2, Carlson J3, McCarthy JB4, Dorsam GP2, Schuh JM2. Hyaluronan stimulates ex vivo B lymphocyte chemotaxis and cytokine production in a murine model of fungal allergic asthma. Immunobiology. 2015 Feb 7. PMID: 25698348.

  • Ghosh S1, Samarasinghe AE, Hoselton SA, Dorsam GP, Schuh JM. Hyaluronan deposition and co-localization with inflammatory cells and collagen in a murine model of fungal allergic asthma. Inflamm Res. 2014 Jun;63(6):475-84. PMID: 24519432.

  • Nikitovic D1, Berdiaki A2, Galbiati V3, Kavasi RM2, Papale A3, Tsatsakis A4, Tzanakakis GN2, Corsini E3. Hyaluronan regulates chemical allergen-induced IL-18 production in human keratinocytes. Toxicol Lett. 2014 Oct 1;232(1):89-97. PMID: 25280773.

  • Fieber C1, Baumann P, Vallon R, Termeer C, Simon JC, Hofmann M, Angel P, Herrlich P, Sleeman JP. Hyaluronan-oligosaccharide-induced transcription of metalloproteases. J Cell Sci. 2004 Jan 15;117(Pt 2):359-67. PMID: 14657275.

  • Campo GM1, Avenoso A, D’Ascola A, Scuruchi M, Prestipino V, Nastasi G, Calatroni A, Campo S. The inhibition of hyaluronan degradation reduced pro-inflammatory cytokines in mouse synovial fibroblasts subjected to collagen-induced arthritis. J Cell Biochem. 2012 Jun;113(6):1852-67. PMID: 22234777.

  • Campo GM1, Avenoso A, D’Ascola A, Prestipino V, Scuruchi M, Nastasi G, Calatroni A, Campo S. 4-mer hyaluronan oligosaccharides stimulate inflammation response in synovial fibroblasts in part via TAK-1 and in part via p38-MAPK. Curr Med Chem. 2013;20(9):1162-72. PMID: 23298137.

  • Liang J1, Jiang D, Jung Y, Xie T, Ingram J, Church T, Degan S, Leonard M, Kraft M, Noble PW. Role of hyaluronan and hyaluronan-binding proteins in human asthma. J Allergy Clin Immunol. 2011 Aug;128(2):403-411. PMID: 21570715.

135 Comments

  1. Nigella Pressland says:

    Hi there, your site is very interesting. I realise this is slightly tangential to the article, but if HA has such big molecules, is there any benefit to applying it externally, other than as a humectant on damaged skin? It seems to be touted by the cosmetic industry as an anti-aging product, but it seems to me that it is just a moisturiser. Your views would be most welcome.

    • drjohn says:

      Excellent question, Nigella. We know that hyaluronic acid (HA) has many functions at all levels within the skin. But since intact (HMW) HA is a very large molecule and not likely to be absorbed in intact skin, what are the benefits to topical application? First, let’s confirm that it is a terrific humectant in that it binds 1,000 times its weight in moisture to the skin. Second, the molecules can be cross-linked to create polymers (films, sheets, or biogels of HA). Third, the HA molecule has binding sites that can hold (and make available) bioactive molecules such as growth factors. Within skin, we have discussed how HA can act as a biosignal and HMW-HA moderates inflammation, but when fragmented in the presence of enzymes those LMW-HA species are inflammatory. In wounded skin, HA is involved in granulation tissue formation and re-epithelialization – critical parts of the healing process. HA also acts as a free radical scavenger deeper in the epidermis and dermis. And all of this also comes with a high degree of “biocompatibility”. Since it is natural, HA is not likely to cause allergic reactions. (If it does, it would be because it is of nonhuman origin and not pure).

      Your question has to do with both normal and “damaged skin” which is a wide spectrum. If the barrier function of the skin is entirely intact, then HA is really a great moisturizer and perhaps nothing more. But even in the presence of small damage (e.g. sun exposure) some of it’s wound healing effects might be taking place. It can provide both a physical protective barrier that protects allowing natural mechanisms to restore from within while preventing dehydration, and also has multiple biochemical roles to play in both minor and more disruptive wounds. We can put microneedling of varying depths on that spectrum as well. Multiple punctate disruptions to the skin’s natural barrier function, or multiple wounds? Which of these descriptors fits is open to debate. But either way, HA can be seen as beneficial. In microneedling, its other benefit is to provide glide when automated pens are being “dragged” across skin.

      As a moisturizer, HA acts quite differently to lipids and other humectants that have better penetration capabilities. But for the very reason of it’s size and molecular weight it perhaps provides a better short term barrier replacement, and of course you mix these types as well. Part of our work is with HA hydrogels which are quite remarkable for covering wounds and delivering growth factors. We are perfecting an HA mask that we like a lot.

  2. Nigella Pressland says:

    Thank you for taking the time to answer. I’m UK based & find it very hard to get any genuine scientific evaluation of the creams (often very expensive) that are sold to be put on the skin. The advertising of most of the cosmetic products is outrageous, in my opinion. I watched a commercial for a cream yesterday that was referred to as “bouncy” and would work over night to help skin appear “well-rested” and “satin smooth”. None of those descriptors actually mean anything, so it is very much a case of caveat emptor, which is easier said than done as an ordinary mortal! However, now I’ve found your site, hopefully I shall be better informed.

  3. Lucas says:

    Hi,

    This is really interesting and what you’re saying makes a lot of sense. But I have rosacea and there have been those in online forums which experienced improvement in their symptoms using a low molecular weight hyaluronic acid gel (bionect), which is marketed towards irritated skin. Have you heard of this product?
    Also, this link (http://jddonline.com/articles/dermatology/S1545961613P0664X/1#close) has been going around, and I don’t have the technical background to judge it.

    Thank you,
    Lucas.

    • drjohn says:

      Hi Lucas – great question. We have seen this report, and it makes no sense to us, logically speaking. Let’s start with these two quotes:

      “Rosacea is a chronic cutaneous disorder that is usually found on the face. The disorder is most commonly characterized by flushing, erythema, telangiectasia, edema, papules, and pustules.1 The cause of this inflammatory disorder is unknown, but is thought to include multiple contributing factors…”

      OK, we can agree with that. Rosacea is an inflammatory disorder. Now they go on to say …

      “As high molecular weight hyaluronic acid (HMW-HA) is depolymerized in sites of inflammation or tissue injury, low molecular weight hyaluronic acid (LMW-HA) fragments result…. In addition, LMW-HA has the ability to alter the innate immune response partly stimulating the production of cytokines and chemokines by macrophages and activating T cells and dendritic cells. Effects on cell behavior include leukocyte, fibroblast, and endothelial cell migration and activation.

      Notice this bolded bit: leukocyte, fibroblast, and endothelial cell migration and activation is the very definition of inflammation.. So, we must ask, how can it be that an inflammatory condition (rosacea) is improved by inflaming skin further? Makes no sense, right?

      Maybe this offers some clue: “Lastly, LMW-HA induces the production of β-defensin 2 (DEFβ2) by stimulating a tissue injury response, ultimately creating an antibacterial effect that allows for regeneration of the cutaneous epithelium and reduction in antigen load”. To the extent that LMW-HA induces defensins (natural antibiotics), and rosacea sometimes responds to antibiotics, this may offer a putative explanation?

      What is also confusing to us is that we in our research clinic see dramatic improvements within days (not 8 weeks as in the study) in rosacea signs and symptoms using a product made with anti-inflammatory cytokines & growth factors derived from mesenchymal stem cells. Tamping down the inflammation works wonders. We should get Dr George to comment on this – he has personal experience.

      Maybe the study above demonstrates a hormesis principle in action – many cells getting killed off due to oxidative stresses results in rapid turnover of fresh epidermis. What doesn’t doesn’t kill you makes you tougher?

      • Firefox7275 says:

        Do you have any comments on the angiogenic effect of low MW hyaluronic acid when it comes to rosacea? Is the eight week duration of that study just not long enough to see this occurring?

        If that is an issue presumably one would want to give low MW hyaluronic acid a particularly wide berth right after IPL treatment for rosacea?

        Thank you.

        • drjohn says:

          Rosacea is a different beast. Recent work on its pathophysiology suggests defects in toll like receptor pathways, and defensins. Now we do know that LMW-HA stimulates those things. That can help in self-defense against bacteria. We know that bacterial overgrowth is part of the rosacea complex. Another place where defensins are critical is vaginal epithelium. We also know that toll like receptor induction with LMW-HA, helping to protect against bacterial overgrowth. So, it may be the same or similar in rosacea. Induction of defensins has benefit. But chronically – not good to hold off aging.

          Vaginal TLR & LMW-HA: http://www.ncbi.nlm.nih.gov/pubmed/21102537

          Rosacea cytokines: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704141/

          This review focuses on the crucial role of HA in vascular integrity and how HA degradation promotes vascular barrier disruption, with low molecular weight fragments causing damage to the endothelial
          glycocalyx.: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253523/pdf/ajcd0001-0200.pdf

    • drgeorge says:

      Hi, Lucas. I echo Drjohn’s comment that the use of LMW-HA to reduce an inflammatory condition such as rosacea is at odds with published studies that show otherwise i.e. LMW-HA tends to promote inflammation. As he suggests, there may be other mechanisms at work. Seldom is something in medicine, particularly a physiologic process with so many contributory components as inflammation, a black or white issue. Confounding variables abound. Perhaps that is why studies often show conflicting results. What he also mentioned is how the net anti-inflammatory pattern of cytokines and growth factors produced by bone marrow mesenchymal stem cells in culture can attenuate inflammation. In that case, the story holds together nicely since they play that role physiologically in the healing and rejuvenation process throughout life. In fact, fetal wound healing is the paradigm of inflammation-free healing, felt to be the result of abundant anti-inflammatory cytokines during the early months of gestation, particularly abundant quantities of TGF-beta3, the quintessential anti-inflammatory cytokine. In my personal experience, my decades-long saga dealing with rosaces (oral doxycycline, topical Metroget and occ. steroids) can to an abrupt and most pleasing end when I started using the skincare product Drjohn and I developed using the cells mentioned above. I discontinued all prescription meds when I started our prototype formula and within a week my issue with rosacea became part of my past. My wife, whose makeup was often purloined to make my face more presentable for social events, was thrilled. I have not had a flare-up since July 1, 2011, the day I started our product. We have since heard numerous other instances of improvements in rosacea symptoms and our products now are used to reduce inflammation and shorten downtime following ablative and semi-ablative facial aesthetic procedures. It’s gratifying when the theory and real-life experience line up so nicely.

  4. Lucas says:

    Hi,

    Thank you for that! It certainly doesn’t make sense to promote inflammation on an already inflammatory process.

    I inadvertently have been using a toner with three (!) different kinds of low molecular weight hyaluronic acid derivatives. I know that because the company has provided that information, but is there anyway to know whether I’m buying something with LMWHa or not? The most common hyaluronic acid salt I see everywhere is sodium hyaluronate. What do you think of that ingredient? What should I look for in the INCI list to make sure I’m not getting the wrong kind of hyaluronic acid?

    Thank you again,
    Lucas.

    • drjohn says:

      Sodium hyaluronate generally is HMW-HA (the good stuff) which is the natural form. If HA has been processed (enzymatically degraded) to produce LMW fragments (extra steps taken in the lab, at extra cost), the company selling it should say so. They use it as a marketing ploy, so it makes no sense for them to put in something that costs more if they aren’t going to advertise it as such. Pure unadulterated sodium hyaluronate or HA is natural, physiologic, so no worries, we like it a lot and use it in our own microneedling solution.

  5. kflab says:

    Dr. John,

    What about taking HA internally via pill form?

    • drjohn says:

      You can take it orally, and yes indeed some of it is absorbed intact and gets into your bloodstream. A small amount gets filtered into e.g. joints, eyes, etc. and some may even make it to skin. About 95% is lost in the urine. Not compelling evidence that it helps skin, but then nothing to suggest it is not safe also. You do get HA (along with other matrix elements & fragments) from gelatin an bone broth and the like – anything derived from animal connective tissues. But in skin care, the best studied role of HA is to sit on the top of skin and draw water to itself to moisturize. best way to get it there is to slather it on.

  6. Luke says:

    This is interesting as almost everything I read points to the low-molecular weight being superior. I’m not sure what to think. Have you seen this study? https://personal-care.evonik.com/product/personal-care/en/media-center/downloads/publications/Documents/sofw-hyacare-50.pdf

    • drjohn says:

      Yes, we have seen that study by the manufacturer. Not published in a peer reviewed journal. It says LMW penetrates better (makes sense). And that it gives quick results by ameliorating wrinkles (which is always our first clue that the mechanism of action is inflammation – since true collagenesis and elastogenesis takes longer than 4 weeks). They call it anti-aging. I call it “pro-aging with benefits”. Analogy: like getting a sun tan. Bronzing by ultraviolet rays may make you look better for a while – but eventually catches up with you and actually accelerates aging in the long run.

      These papers (amongst many others in the medical literature ) paint a different picture:

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985537/
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106675/
      http://www.ncbi.nlm.nih.gov/pubmed/18641349

      To put it succinctly – HMW-HA associated with scar free healing & regeneration while LMW-HA associated with inflammation & scarring.

  7. Louise B Andrew says:

    Very interesting.
    FWIW, the above citations both refer to the same article.

    The cited article also defines TGF to mean “Tumor Growth Factor”.
    I believe it should be Transforming Growth Factor? Surely these are not synonyms.

    Unless I missed something, nothing was said about the advantage of healing in a nice bath of amniotic fluid. Perhaps we should be capturing this liquid gold? (JK—apparently it would have to be had at an early period of gestation to get the best healing—so lots of moral reservations)

    But seriously, where does TGF beta 3 come from (other than fetal platelets)? Is that the miracle cure for scarless healing?

    • drjohn says:

      Fixed the refs. Good find Louise and you are 100% correct about TGF (T = “transforming” not “tumor”). TGF beta3 is indeed the key to scarless healing. And while human amniotic fluid may be a good place to find some, that source has issues. meanwhile, we now know that mesenchymal stem cells in culture can produce this en masse. That is also part of the answer “where does TGF-beta3 come from? During embryonic life, many different types of cells are behaving like these stem cells (indeed embryos are by their nature mainly stem cells – makes sense from a developmental perspective). So during fetal life skin and other tissues make a lot of their own TGF beta-3 driven by the genetic imperative to develop into a infant human capable of surviving outside the womb. We gradually lose that capability over time (a strong correlate of aging itself). In adults, much of human regenerative capacity resides in these very special cells that live in the bone marrow but patrol the whole body looking for problems to solve (e.g. wound healing). And because cytokines are a communication molecule, these stem cells not only tell other =cells what to do (e.g.make new healthy tissue) but also tell them to make more of the same molecule. Sort of a “tell a friend” scheme that amplifies the message in that tissue. There are other cytokines that tell tissue to grow, but TGF beta3 is unique in its ability to create scar-free (fetal-like) regeneration. Hope this sheds more light on the “where does it come from” question.

  8. Elizabeth says:

    Is hydrolized hyaluronic acid the same as the LMW stuff talked about here? Also, HA serums being so popular are readily available in so many different price points that you eventually want to believe when one person says it’s such a “high quality” one that you should pay $150 for it; for example, Bakel HA serum. When you see most of the Japanese toning lotions and milks containing hydrolized hyaluronic for the low price point, on the other end, of course butylene glycol being a main ingredient in a lot of those products too which I’m not convinced helps.

    • drjohn says:

      Elizabeth – yes, the way to break up HA into fragments is by hydrolysis. And you are right about the price. You can buy “pure HA” on Amazon for about $5/oz. But read the label to make sure it is in fact pure and not containing other stuff. Remember, HA sits on the surface of the skin and provides a moisture barrier. But it also can be a superb carrier or delivery system for molecules that normally attach to HA (e.g. many growth factors and cytokines). I also like HA masks.

  9. Neil Mosunic says:

    Hello Dr. John,

    Thank you so much for your work and replying to comments. I’m considering taking HA to see if it would help with what I believe to be the early stages of elbow tendonitis (from climbing, which I’ve gathered is medial, like golfer’s elbow, opposed to lateral, which is tennis elbow).

    Are there any specific brands of HA capsules you would recommend for this? Is low molecular the best option for this? I’ve seen claims that some brands have low molecular from sodium, is this just marketing or is it as effective as low molecular from animal sources? I would like to get non-animal source if I can find one that is as effective, but if not, I would go for an animal sourced version.

    Thanks in advanced. Have a great day and keep up the research for those of us who really try to inform ourselves!

  10. Sam says:

    I’ve read some articles (nothing scientific) stating that pure HA can dehydrate the skin in certain climates because if there isn’t enough moisture in the air that the HA draws moisture from your skin to itself. Is there any truth to these claims and if so is it possible to avoid. Second question, if using other oils topically, like vitamin, is it best to put HA on first or afterward?

    • drjohn says:

      Sam, we have seen this a lot too, but you are right – nothing scientific. Welcome to the skin trade. While it is true that HA loves water, once it is saturated it is not going to act as a desiccant (drying agent). Generally the HA you buy is actually less than 1% HA and the rest is water (and maybe other stuff). If you pace pure diluted HA on skin, some water will evaporate at the surface. This can make skin feel dry, but the HA is still acting as a water loss barrier, keep the skin underneath happy. The proof would be found in a TEWL meter (trans-epidermal water loss). We should do an experiment. HA also can spontaneously cross link (form natural weaves), which can lead to some temporary tightening as the molecules actually form matrix-like meshes on the skin surface. BTW – you can always put a moisturizing cream on top of HA (not after microneedling though).

  11. Jae Z says:

    Hi Drs. John and George,

    Dr. John says in response to Lucas that you guys use HA in your microneedling solution. I think you’re referring to the Palmitoyl tetrapeptide-7 in Ante AGE MD, right?

    I would REALLY REALLY love clarification on some of the info on the Ante AGE MD product line website:

    On the Accelerator MD page, it says “Its powerful ingredients also make it the perfect post-procedure topical adjuvant following laser, microneedling, abrasive, and other ablative or collagen inducting medical esthetic treatments.” But when I look at the ingredients list, it doesn’t seem to have what you’ve recommended in your blog, e.g. only physiologic ingredients, in particular cytokines and GF derived from adult human mesenchymal bone marrow stem cells and HMW HA. Those ingredients do appear in the Serum MD page, which makes me think that actually THAT is intended as the immediate post-needling product? The Serum MD page also features the quote “Its powerful ingredients also make it the perfect post-procedure topical adjuvant following laser, microneedling, abrasive, and other ablative or collagen inducting medical esthetic treatments.”. I’m wondering if the appearance of that quote on the Accelerator MD page is a copy-pasta typo/ error? Would you mind clarifying, is Ante AGE MD Serum recommended for immediate post-needling application, even after more intense medical needling? Only after more shallow depths? Or is it recommended for later application, after the window of highest post-needling absorption closes? When should Ante AGE MD accelerator be applied?Additionally, I’ve been wondering about this – the MD formulations seem like better, stronger versions of the regular Ante AGE products. Is that true? If so, why sell the regular Ante AGE line at all? Why not only sell the more effective version (MD)?

    Thank you very much!

    • drjohn says:

      Hi Jae Z. There is HA (high molecular weight only) in the microneedling solution, along with cytokines and growth factors, but no peptides. AnteAge MD is a different (daily use, twice a day) product. The only ingredients we allow during and for 4 hours after microneedling are those which are entirely natural (native) to the human body. Peptides are not.

      The AnteAge MD line is only available through physicians. Consider it like a prescription strength medication where a lower dose is available as an over the counter version (regular AnteAge).

      There is not yet an AnteAge consumer version of microneedling solution but I think there is one coming soon.

      AnteAge (serum and accelerator) whether MD or not, is applied twice a day, morning and evening. For microneedling we now recommend using AnteAge for as few weeks before starting medical microneedling. The microneedling solution is applied during the needling session, and then again (by you) about an hour after the procedure. You wait another few hours before putting AnteAge (or anything other than the MN solution) on your face.

      We are seeing spectacular results with microneedling plus stem cell derived growth factors and cytokines for all sorts of skin conditions as well as general anti-aging effects.

  12. Leeanne says:

    Hello,
    When you say HA or hyaluronic acid, are you also saying that sodium hyaluronate is a bad thing and that because it is low molecular weight, it should be avoided? What is the difference between hyaluronic acid and sodium hyaluronate? Isn’t SH the salt of hyaluronic acid so SH would be considered a safe alternative?

    • drjohn says:

      Hi Leeanne. No, sodium hyaluronate is merely the sodium salt. It’s not which salt is involved that matters, it is the size of the HA itself. If it has been enzymatically broken into smaller bits (a process called hydrolysis), e.g. using hyaluronate, that is when it becomes problematic. The other cells consider these fragments to be danger signals, and go into retreat mode, including slowing down or stopping protein production. Such enzymes are part of tissue breakdown, not tissue building. Any salt of HA (sodium or potassium) is quite safe. It’s the HA fragments that are the issue, not salt type.

  13. Hi. I am about to make my own HA 1% serum (using water with the HA). I bought HMW-HA because I had heard of the inflammation low molecular weight could cause in the skin. I’m guessing my serum is not going to penetrate the skin though. Am I just making a barrier that will set on top of my skin? Will any of it penetrate? I’m looking for added moisture as well as some anti aging benefits and I’m starting to think HA isn’t the answer. Thanks!

    • drjohn says:

      You don’t want HA to penetrate your skin. The value of HMW-HA applied topically is that it is too big to be absorbed but holds water like crazy for hydration while forming an effective barrier. Damaged barrier function is the culprit in many common skin irritations, allergies, and the like. It also leads to an aged appearance. LMW-HA is more likely to be absorbed, but has the negative effects mention in the post. HA alone may not be anti-aging in the true, regenerative sense of the word. But keeping skin well hydrated is a big part of the battle at any age. It’s not the whole answer, but is a great start. Bravo for mixing your own – its relatively simple and inexpensive. But keep in mind that without a preservative it is going to have a limited shelf life. Best to mix small batches regularly, paying attention to a clean environment and tools. Keep your DIY mixture in the refrigerator between uses.

  14. Kristi says:

    Hi Dr. John,
    Does your company sell HMW-HA yet? If not, what brand is reliable to use during and post needling? I have looked on Amazon and its very overwhelming. Thanks in advance!

    • drjohn says:

      Cellese only sells growth factor and stem cytokine based products, although we find HA to be a superior molecular host and hydration factor in our products. You can buy The Original Hyaluronic Acid Serum 100% Pure 2 oz. from Timeless Skin Care on Amazon for $9.98 with free delivery. A bargain. It’s not hydrolyzed so it is all HMW. The preservatives are not ones we consider to be troublemakers.

  15. Curious says:

    I have never seen this before. I went at looked at some products that I have and I am wondering if a product says that it has short and long chain HA are they saying the same thing? That short chain HA = low molecular weight HA and long chain HA is regular or high molecular weight HA?

  16. Kristi says:

    Thanks for your reply, Dr. John! Also wanted your thoughts on the micro current device Nuface and led red light for increased collagen. Seems that there are claims of research of accumulative effects of micro current by increasing ATP in the cells. And some studies seem to support led red light therapy. Many thanks!!!!!

    • drjohn says:

      Kristi, we have read many user reviews of NuFace that raise red flags: burns, landing strips, hyperpigmentation and the like. Of course electrical stimulation (ES) has a long track record in wound healing, and higher current RF devices in medical aesthetics (physician offices) product stellar results. . Microcurrent ES (MES) is less well established and in fact there is little clinical evidence for efficacy. Here is an excellent published review that says the same thing. Of note, NuFace doesn’t tell you their current parameters, and their study results or not anywhere to be found, so making comparisons with known science is difficult. However, low level current is also the basis for iontophoresis, which is a process whereby ionic molecules (actives) in a topical serum can be drawn into the skin (much better absorption). So, what does NuFace sell to go along with its iontophoretic MES device? Plant stem cell malarky – worthless nostrums based on blatant pseudoscience. Our advice is that you should never trust a purveyor of skin care who cannot tell the difference.

      Of note on a theoretical level: ES works by stimulating growth factors associated with early stages of wound healing, most prominently VEGF. VEGF promotes angiogenesis (new blood vessels) tends to be inflammatory. You may get more collagen, but it won’t be the pretty basket weave kind.

      We like iontophoresis, but we don’t like plant stem cell fiction, burns, inflammation and hyperpigmentation. If anyone has the wave form, pulsing, current type and other data for NuFace please send it our way.

  17. Kristi says:

    Wow!!! Thanks for the info, now could I please bother you on your thoughts about the red led light home units? Helpful or harmful? Different models have different wavelengths of light. I started using AnteAge skincare and wanted to do something non invasive to up the ante!!! Thought about micro needling and I have some autoimmune issues and am a bit hesitate to open those skin channels after reading about all the immune issues some folks are having with products. Even wondering if the preservatives in the pure HA could be bothersome.

    • drjohn says:

      The literature on LED therapy is generally quite good. Here is a recently published excellent review of the scientific literature on the matter of LED’s in dermatology. Red light can be both anti-inflammatory and regenerative. The effect is amplified in the presence of biochemical stimuli. Indeed we have had reports of users of red light plus AnteAge who found the combination to be quite effective. We are contemplating a clinical trial to document the effects of combined GF plus red light.

      Have I mentioned yet that there is now a research clinic in Newport Beach, CA devoted to aesthetics clinical research, with an emphasis of combining stem cytokine and growth factors with other modalities such as microneedling, laser, RF, LED, iontophoresis, ultrasound?. Any folks who live in the Orange County area who are interested can contact docs@barefacedtruth.com for information about ongoing studies. There is one starting up this week that studies hair restoration using a special cytokine/GF mixture along with microneedling with a new type of pen.

  18. Curious says:

    Thank you so much Dr. John! I was confused because of the way they worded that.

    • drjohn says:

      BTW – there is new research out that furthers the argument we make about the inflammatory nature of LMW-HA, and the mechanism of action includes the activation of macrophages (tissue eating white cells). Also if you look at fetal wounds vs adult wounds you see a marked difference. Fetal wounds (scare free non-inflammatory healing) have essentially zero LMW-HA present, while older adult wounds (scarring, inflammatory) have a mix of LMW and HMW hyaluronic acid molecules. The evidence is overwhelming.

  19. JM says:

    This is going to sound far fetched probably, but, I was researching LMW HA because after using it one time on my face, neck, and hands I experienced sore joints and nerve type pain in my hands and up through my wrists; and my face felt numb. It was bizarre. I have experienced this type of sensation once before while taking the supplement quercetin. It turned out that quercetin can cause inflammation so I had an answer for my pain which I was beginning to worry was RA. I am going to assume the LMW HA I used caused instant inflammation; but that almost seems impossible. Thank you for the information. It’s disappointing to find out that the miracle wrinkle cure isn’t a miracle after all.

    • drjohn says:

      JM, not so far fetched. Injection of HA into joints for therapeutic effects has been investigated quite a bit. The consensus is that HMW-HA is clinically more beneficial than LMW-HA. Further, if you look at inflammatory markers you see that they are much higher when LMW-HA is used. HA with a high molecular weight is more effective in downregulating proinflammatory cytokines such as interleukin-1beta and tumor necrosis factor-alpha. Quercitin has well known anti-inflammatory properties so i cannot make sense of that reaction.

  20. KK says:

    What about HA for vaginal dryness and absorption in your stomach?
    Somewhere, I read HA is good. Now I am reading this and I am confused with the technical words.
    Please, Is it HA good for Vaginal dryness?, What works the best, oral or topically? Can you recommend a brand? where can I get it?

    • drjohn says:

      Hi KK, HA is well proven in medical studies to be an excellent antidote to vaginal dryness. Both oral and intravaginal work, but intravaginal gets you higher exposure so works better. Hyalofemme is a product with HA only, available on Amazon.

      It is also well known that a particular growth factor (KGF) has a remarkable effect on thinned vaginal epithelium to regenerate it to a more normal state (safely). We have in fact now put together a product combining HA with KGF for vaginal rejuvenation (also for vulva). We call if RejuVV, currently in clinical testing.

  21. LW says:

    Thank you for all of this information. So please correct me if I have misunderstood but from what I have gathered from the article and comments that it is better to avoid the use of LMW HA and just stick with the HMW HA as a way to improve the moisture in the skin? Because the LMW HA can cause inflammation to occur. Also, I am very confused by the percentage amounts different companies quote for their HA. One will say theirs is 25% (professional use, not sold retail) while another is 2%. They seem so far apart, do you have any insight into this?

    • drjohn says:

      Yes, yes, and … hyaluronic acid comes in bulk as a solid which is then dissolved in water to become an HA solution. The standard solution for HA is 1% (that is, 1 gm per 100 ml) and anything much higher than that makes a solution that is too viscious to be usable. I believe that when folks say 25% HA they really mean 25% of a 1% solution (i.e. 1% diluted 4:1 with water). 50% would be a 2:1 dilution, etc. Nothing else makes sense.

  22. gm says:

    Hello,

    Thank you for sharing your knowledge with us.

    Are there certain cosmetic ingredients or environmental conditions that may cause HMW-HA to fragment into the inflammatory LMW-HA species? E.g.s: (1) Does combining HMW-HA with AHAs present this risk? (2) Does wearing HMW-HA in sunlight present this risk?

    • drjohn says:

      The fragmentation is caused by enzymes call hyaluronidases. Things that cause inflammation in the dermis would increase the production of these enzymes. So, to the extent sunlight or acids cause inflammation they would indirectly cause fragmentation through production of hyaluronidases. Ascorbyl palmitate variants have been shown to inhibit hyaluronidase. The work is early but if true would be a good reason to put this in anti-aging skin care formulations.

  23. gm says:

    Thanks for your reply – your knowledge is much appreciated.

    Is degradation of HMW-HA into LMW-HA, via oxidising agents, worth considering?

    Also, is degradation of HMW-HA by ascorbic acid worth considering?

    Often, HA skin care products contain many ingredients, and I am concerned that some of these don’t play nicely with HMW-HA.

    • drjohn says:

      It really is an enzymatic process (proteases) so I’m not worried about oxidation per se causing HA fragments. Although oxidation can cause release of proteases within the matrix. Vit. C as an antioxidant in a non-inflammatory form and dose could only help. The things that don’t play well are things causing inflammation.

  24. Yves says:

    I would be curious to hear your response to the comment from “jm” dated Dec 8, 2015. Thanks!

  25. yolly says:

    I am curious as to what you think of this company and their serums? Are they really what they say they are on the tin?!

    • drjohn says:

      http://episilkserum.com/pha_serum.html. I think this company is completely “science impaired”. I have no trust in anything they sell. Here’s why: They hawk a product called Renu-Age. Said product is claimed to “improve microcirculation”. They source the ingredient from Pentapharm, one of those dubious Swiss cosmeceutical houses. Here is what Pentapharm has to say: Efficacy tests – In vitro tests (aPTT-activated Partial Thromboplastin Time and TT-Thrombin Time) have shown that REGU®-AGE improves the microcirculation. Oh, really? Any 1st year med or nursing pharm student will tell you that PTT and PT are tests that measure blood clotting, not microcirculation. If they indeed are modifying PT and PTT then they are causing blood clots or a tendency to bleed. Either would be dangerous. Of course it is unlikely that the substance does so, but it shows the total and complete lack of even basic knowledge of physiology, or a tendency to deceive by just pulling some acronym test name out of a hat and pretend they even know what it means. This is the worst kind of example of the snake oil salesmen of the cosmetic industry. I point to those egregious European ingredients suppliers and marketers who think we are all too stupid to know anything, so they can say whatever they want. Sheep being led to the slaughter. Really niggles me. Can you tell?

  26. KL says:

    If HA is degraded into smaller fragments at the site of inflammation, wouldn’t applying topical HMW HA to an inflamed skin instigate the inflammatory cascade, particularly in a rosacea skin or skin that has been microneedled?

    • drjohn says:

      Great nerdy question. Here is the ultra nerdy answer. No – because HWM-HA actually counteracts the effects of LMW-HA. Here’s why – the skin is abundant in cells that express CD44. This is a cell surface receptor involved with inflammation on/off through TLR (toll like receptors). While LMW-HA can attach, stimulating inflammation, HMW-HA attaches but forma a sort of film that coats the surface to then prevent LMW-HA from attaching. It’s very cool! Now, if you have a lot of hylaluronidase around (the natural enzyme that breaks down HMW into LMW-HA) some will become fragmented. But it’s a game of numbers. If the balance is in favor of HMW-HA, anti-inflammation wins over inflammatory responses. Small puncture wounds don’t require much in the way of inflammation for healing. You want to tip the balance there quickly. Rosacea is a chronic self-perpetuating inflammatory disorder, and there you want to tamp it down permanently.

      If you want really nerdy you may want to scan this paper: http://www.woundsresearch.com/article/hyaluronic-acid-inflammation-and-tissue-regeneration#sthash.CyuN08Ys.dpuf

      Excerpts:

      “In physiological conditions, the activation of immune system cells is crucial for proper wound healing. In acute wounds, small hyaluronan fragments accumulating at the site of injury activate the immune system to manage rupture in tissue integrity; however, in chronic wounds a constant excessive inflammatory response proves to be a negative phenomenon that actually prevents that wound from healing. ”

      “Several studies have concentrated on TLRs and TLR signaling as a key player responsible for proinflammatory properties of LMWHA. Several authors have confirmed, using in vitro studies, that LMWHA is able to bind to TLR receptors and consequently initiate the signaling cascade, leading to the production of proinflammatory cytokines and chemokines in various types of cells.46 In immune cells from injured tissues, TLR2 and TLR4 activation by LMWHA leads to initiation of MyD88-dependent NFκB signaling cascade and pro-inflammatory cytokine gene expression.14,47 Iwata and coauthors48 have shown that LMWHA stimulates B lymphocytes via TLR4 receptor to IL-6 and TGF beta production. Induction by LMWHA TLR-related myeloid differentiation primary response gene 88 (MyD88)/NFκB signaling was also confirmed in breast tumor cells. Bourguignon et al49 have shown that small HA fragments stimulate CD44 association with TLR2, TLR4, and MyD88, leading to NF-κB-specific transcriptional activation and the expression of proinflammatory cytokines IL-1β and IL-8 in the human breast cell line. Taken together, these reports suggest that LMWHA induces inflammation via activation of TLR receptors and initiation of MyD88/NFκB signaling which leads to production of proinflammatory cytokines and chemokines.”

  27. KL says:

    I was playing devils advocate. I’m writing an article on the benefits of HMW HA in rosacea skin, and was looking for any possible argument against its use by a clinician 🙂 Thanks for talking nerdy to me.. lol

    • drgeorge says:

      KL, in checking Google Scholar and PubMed, there are numerous articles wherein HA is described as part of topical formulations for various topical treatments for rosacea. The issue, then, is there an optimal molecular weight HA to use for this purpose. As Drjohn pointed out in his article, low molecular HA is pro-inflammatory whereas high molecular weight HA has the opposite effect. Based on that fact, it seems high molecular weight HA is preferable in rosacea skin. That is, however, not the complete story. Two studies cited below, demonstrated improvement in rosacea and seborrheic dermatitis using low molecular weight HA salt gel. We do not, however, see studies arguing against the use of high molecular HA in rosacea.

      JJ Drugs Dermatol. 2013 Jun 1;12(6):664-7.
      Efficacy and tolerability of low molecular weight hyaluronic acid sodium salt 0.2% cream in rosacea.Clin Aesthet Dermatol. 2014 May;7(5):15-8.

      J Clin Aesthet Dermatol. 2014 May;7(5):15-8Efficacy and safety of a low molecular weight hyaluronic Acid topical gel in the treatment of facial seborrheic dermatitis final report.

  28. Bj says:

    Hi, I am a little confused.
    I stumbled on this article due to skincare product confusion. I have been using devita skin care natural vegan products. I use pretty much the whole skin care line and love them. I’m using a particular product by devita skincare that I really enjoy atleast it feels good on my skin it is the hyaluronic surugel it is supposed to be 1percent hyaluronic acid and it just says vegan source. Well I just turned 30 and as we humans do when we reach age milestones I am imagining my face is falling,my pores are enlarging,my wrinkles are starting and I must turn back the clock lol:) So I started investigating stronger more chemically laden beauty products and I am so confused by alot of things because all of these companies have their own hook. “Use mine cause its natural, use mine because its scientifically advanced, use mine because its expensive or inexpensive” you get the picture. Even the simple thing like hyaluronic acid…
    I found a bellevolve advanced hyaluronic serum containing both hydrolized nano form and a sodium hylaronate they make it sound terrific but that’s marketings job so I’m confused is that bad or good. Is it ok to stick with natural skin care products and vegan sources of hyalauronic acid or are they ripping me off?should I step up to more advanced science and “proven” chemically laden products?

    • drgeorge says:

      For many reasons, the topical skincare world is perhaps the most crowded and confusing of them all. It’s the perfect alignment of demand (everyone wants to look better and slow the aging clock, particularly women), unwary consumers (very few people have the knowledge and background to make informed discerning judgments about ingredients), marketing chicanery (outright lies and fantasies, admittedly once in a while with an occasional kernel of truth), and HUGE profit opportunities (even if the consumer only buys your product once.) Throw in the fact that every famous pretty face wants in on the action, and it makes the wild west look tame.

      Hyaluronic acid, in one form or another is found in many products because it is such a great hydrator, and plump moist skin looks better than dry skin with less volume. It’s also a natural molecule easily tolerated by everyone. Drjohn discussed the molecular size aspect, and the potential for promoting inflammation, so his advise is a good reference regarding HA. But your question goes further.

      Active ingredients that have proven published benefits when used on the skin are the direction you want to go, especially as you head into your 30’s and beyond. Spend some time reading about the ones that comprise the dermatologists’ pyramid of skin health and beauty. Of course, sun protection is #1 regardless of age and use it everyday! Then comes AHA and BHA (acids that promote exfoliation), Vit A (Retin-A, retinol, etc.), Vit C, Vit E, niacinamide, green tea, resveratrol grape seed oil, curcuminoids (from tumeric), isoflavones, ceramides, linoleic acid, and most recently added, growth factors and cytokines from human stem cell culture.

      Getting them all and using them will break the bank and eat up half your day, so look for products that contain multiple actives. Your BFT hosts, drjohn and drgeorge, developed one you may want to consider that we think is best in breed. Email us if you want to learn more about it.

  29. CR says:

    I do microneedling and use SkinCeuticals Hydrating B5 Gel as a glide. Would this be appropriate and safe? The ingredients in order are Water, Sodium Hyaluronate, Panothenic Acid, and Phenoxyethanol.

    • drgeorge says:

      We are not fans of using anything for microneedling that in not found naturally WITHIN the skin so HA and normal saline make the cut. So do microneedling solutions formulated for that purpose that contain natural growth factors and cytokines with the caveat being they should REDUCE inflammation. For a deep dive into microneedling science, we strongly recommend The Concise Guide to Dermal Needling by Dr. Lance Setterfield.

      Here at BFT, we see some nasty reactions from people who have tried non-physiologic ingredients like the so-called snail growth factors, covered in depth in posts here on BFT. We are also aware of skin reactions to serums containing copper peptides and Vitamin C. We can’t say for certain which ingredient in these products is the culprit because there are several that are NOT physiologic nor found naturally in the skin. I suggest you read our posts here and stay cautious. If you would like to learn more about the product your BFT hosts formulated in consultation with Dr. Setterfield, send us an email. We are not aware of any reactions and the number of applications is approaching 100,000.

  30. Kim says:

    Hi Dr John/George

    I have eczema and ligament inflammation in the knee (arthritis?) and degeneration of the metarsophalangeal joints.

    1) for eczema = what type of HA to apply (HMW?)
    2) for arthritis and degeneration of joints = what type of HA to
    consume and how much at one time?

    3) There is a type of HA Oliga = Is it better than HMW?

    4) Any side effects for consuming Na Hyaluronate powder?
    I read that Stanford Chemicals is selling them but I do not know
    their quality?

    Also, Bulk supplements are selling Sodium Hyaluronate powder with numerous good reviews.
    Any idea?

    I have not bought any yet as I want to buy the correct type and quality?

    Thanks so much

    • drgeorge says:

      Thanks for your questions, Kim. In eczema, the anti-inflammatory effect of high molecular weight as opposed to other size molecules makes it a preferable choice. Inflammation is the major component In fact, I just ran across an article where HA has shown anti-inflammatory benefit in gingival (gum) treatment for periodontal disease. Worth a try for sure.

      As far as its use in arthritis is concerned, oral radioactive tagged high molecular weight HA was fed to rats and dogs. Most (86.7 to 95.6%) was excreted in urine and feces, almost all in the feces. There was, however, evidence that radioactive uptake was present in skin, bone, and joint tissue at 24 hours. A different study in rats with oral and injected radioactive tagged HA showed up to 90% was absorbed from the digestive tract and used as an energy source or a structural constituent of tissues. The tissue that showed the majority of deposition was the skin, not the joints.

      The above makes BFT extremely skeptical of the efficacy of HA in arthritis. I am certain the marketing materials used to sell such products would have a completely different message. If you have access to what scientific claims they make, and the studies used to substantiate those claims, we would love you to share. Our bottom line at this juncture, save your money until the science is clear and convincing – to you and to us.

      While there is well documented proof of efficacy of intra-articular injected HA in osteoarthritis, the lack of

  31. Stephen says:

    Hi,

    Regarding HMW Hyaluronic acid what molecular weight in kDa would you recommend using?

    The following articles suggest that 50kDa has the benefit of topical absorption without the pro-inflammatory effects. Do you agree with this? Thank you.

    Stephen

    Farwick M, Gauglitz G, Pavicic T, Köhler T, Wegmann M, Schwach-Abdellaoui K, et al. Fifty-kDa hyaluronic acid upregulates some epidermal genes without changing TNF-α expression in reconstituted epidermis. Skin pharmacology and physiology. 2011;24[4]:210-7.

    Farwick M, Lersch P, Strutz G. Low molecular weight hyaluronic acid: its effects on epidermal gene expression & skin ageing. SÖFW Journal. 2008;134[11]:17.

    • drjohn says:

      Hi Stephen, this article makes conclusions from its own data that I disagree with. It states “no pro-inflammatory effects” and yet TNF-alpha (a very inflammatory cytokine) is elevated both at 20kDa and 50 kDa HA sizes. Here is the graph from that paper:

    • drjohn says:

      Stephen, the article makes conclusions that are in conflict with the data they themselves present. Look at this graph:

      TNF-alpha

      Clearly TNF-alpha is elevated to at least twice normal at both the 20kDa and 50 kDa HA sizes. TNF-alpha is a highly inflammatory cytokine. Only when you get to 360kDa (LMW) do you see it return to baseline. The gene expression itself looks “defensive” – the skin is trying to create a barrier against a stress or invader. They should have measured matrix synthetic genes.

  32. Candice says:

    Hello Hi Dr John/George,

    Can you tell me what you think of Paula’s Choice Resist Hyaluronic Acid Booster? She uses Sodium Hyaluronate and Hyaluronic Acid in the HA Booster. Not sure if the HA in the product is LMW HA. http://www.paulaschoice.com/shop/skin-care-categories/targeted-treatments/_/Resist-Hyaluronic-Acid-Booster

    Also, can you tell me if the problem with the Hylamide Booster Low-Molecular HA is the inclusion of Hydrolyzed Sodium Hyaluronate, not the Sodium Hyaluronate Crosspolymer? http://hylamide.com/product/booster-low-molecular-ha-30ml

    And why do companies that seem to be innovative like Hylamide/NIOD contain LMW HA in their products if it is problematic?

    Thanks

    • drjohn says:

      I think Paula’s in the good stuff (HMW). The problem with any lysed HA is the signaling nature of the fragments which turn down your own collagen synthesis. To cross link a LMW HA is silly in the first place, since the supposed reason for making in LMW is to allow it to absorb, while cross linking does the opposite and assures it will not be absorbed.

  33. Matt says:

    Interesting article, yet it seems that LMW-HA is considered safe to use in other quarters, which makes me a little confused.

    What is your opinion on this study that showed a number of beneficial effects of LMW-HA?

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970829/

    • drjohn says:

      Matt, this paper doesn’t seem to be a bout LMW-HA, but since it never mentions MW at all, only size of molecules (nano) we can’t be sure. But since it explicitly states they “reduce the size of HA molecules without disturbing their constituent subunit structure” we will assume that no hydrolysis or fragmentation takes place. Sounds more like a new de novo synthesis in the lab. Since all molecules are nano anyway, it makes even less sense. Lost in translation?

  34. kelly says:

    Are any of the ingredients used in the Ante Age products considered “hormones”? I stay away from hormones because I develop melasma easily on my face.

  35. G says:

    Regarding the Paula’s Choice product above, it does contain low molecular weight HA (as do other products of hers). This info is given under the FAQ section for that product, under the question “What is the difference between sodium hyaluronate and hyaluronic acid?”.

    Many companies use LMW HA but call it sodium hyaluronate in the ingredients list. I always ask companies what version of HA they use, and most of the time they say LMW. Very annoying.

    • drjohn says:

      Sodium hyaluronate is the sodium salt of HA. Making a salt form has nothing to do with MW per se, it is more a way to “clean up” the native molecule which tends to bind lots of stuff like lipids, proteins, etc. But it is still native HA -as opposed to fragmented HA (LMW) which happens when you add a digestive enzyme (hyaluronidase). Paula (well really her hirelings – she just reads what they write) seems to think sodium hyaluronate will penetrate skin, but this is incorrect. It is still a huge molecule. But that’s OK because its benefit happens right there anyway – on top of skin – proving a natural barrier.

      • aliha says:

        Hello, Thanks for the really informative article. Regarding HMW Hyaluronic acid what molecular weight in kDa would you recommend using? I have found one at Amazon.com from bulk supplements. It is described as pure Hyaluronic acid-(Na Hyaluronate) (verified in lab) and although the moelcular weight is not mentioned, when contacted they described it as 0.8 MilliThe powder does convert into thin gel like sonsistency when dissolved in cold atrer (in contrast to LMW HA which does not form gel when mixed in water). Any help would be really appreciated. Thanks

  36. Tess says:

    Wow! I came across this article because I had read about the ‘Asian beauty regimen’ and how HA is important in the use of pne having dry skin.
    I’ve never read your blog or anything else: so for a 37 yo female with some sensitivity and dry skin and just having started to research what I need to do face-wise/age-wise – can you tell me about skinmedica aha/bha and HA products? Yay or nay? I’m also ingesting 1000mg of vitamin C and 2300mg of evening primrose oil which the oil seems to have really helped ‘plump’ my skin? Any info is greatly appreciated – here’s the links to the skinmedica products: http://ha5.skinmedica.com and https://www.skinmedica.com/aha-bha-cream.html If these are not recommended, I saw in one of the threads you recommended a ‘pure HA for $5 per oz on Amazon – can you please give the name? And what recommendations on BHA /AHA (any combo pairing for me is questionable) can you comment on what would be better? I’ve been reading on Paula’s choice and she’s not a fan of the BHA /AHA at all – would love to hear your thoughts ??

    • drjohn says:

      Tess, I’m also not a fan of HA/AHA (irrational combo) and while I respect SkinMedica’s roots and good science of the past, I find the HA5 product to be reflective of new people being in charge at SkinMedica. We are now seeing a trend to form over substance, and marketing over science. Sad indeed. See review of GA5 in response to Martha’s question, above.

  37. Tess says:

    Also – what do you make of the Danne montague King line- cannot find a decent review on it due to it being deemed ‘paramedical’ – and I’ve also been using it for years and getting the cinnamon facial and the alkaline facial – thank you!

    • drjohn says:

      Tess, quacky sounding enzyme stuff, to be sure. Enzymes chew stuff up – our bodies internal garbage disposals. One does not “dissolve” scars with enzymes – you might deepen them! Enzymes (luckily) are short lived on skin, as they are neutralized by the skins production of its primary defense system – endogenous enzymes called proteases which rapidly dispose enzymes and other proteins that land on our skin.

  38. Kelly says:

    My Ante-Age duo is on its way!

    What should my AM and PM skin routine be then? (Currently–AM: cleanser, vit C serum, moisturizer, Tizo sunblock.
    PM: cleanser, Obagi 5 blender with Refissa)
    Thank you

  39. G says:

    Paula’s product also contains fragmented HA though – it has both HMW and LMW HA.

    As you said above, sodium hyaluronate contains native (HMW) HA. But some companies list ‘sodium hyaluronate’ in the ingredients list when they have in fact used fragmented (LMW) HA. I know this because I have emailed some companies to clarify what their ‘sodium hyaluronate’ refers to. Are these companies mislabelling their products, or am I misunderstanding something?

    • drjohn says:

      They are misleading, because they they themselves are mislead. So many “formulators” in this industry have no training whatsoever in biologic sciences, skin physiology, or biochemistry. More art than science. We have provided more than ample evidence of the untoward effects of HA fragments, so-called LMW-HA, especially when you get down below 150kD. Published studies abounds. Does nobody read, or understand, the scientific literature?

  40. tariq says:

    does anyone know where i can by very high weight HA for oral use?

  41. Zen says:

    Hello and thank you for the wonderful article!
    I may have missed it, but what is considered a high weight and what is considered a low weight? For example, I purchased a “mix” of weights, but with nothing to compare it to, I’m not really sure what is considered a “high” weight and what is considered a “low” weight, generally speaking .
    200k – Penetrates deep into the skin, healing and hydrating (this almost frightens me in light of your post)
    500k – Penetrates into the top layers of skin to promote elasticity and hydration.
    800k – Works with the top layer of skin to create a protective, hydrating layer; holding in moisture, balancing pH, and maintaining elasticity.
    Thank you so much for your wonderful blog. I’m already hooked!

    • drjohn says:

      See answer to Ritu below. By “k” I believe you mean kDa (daltons, or kiloDaltons to be precise). For proteins, 50 daltons is considered too big. So even 200kD would be huge. (this ignores all sorts of tricks available to cloak molecules so they get through the barrier – not used here – subject of a post in the future).

  42. Ritu says:

    Hello, Thanks for the really informative article. Regarding HMW Hyaluronic acid what molecular weight in kDa would you recommend using? I have found one at Amazon.com from bulk supplements. It is described as pure Hyaluronic acid-(Na Hyaluronate) (verified in lab) and although the moelcular weight is not mentioned, when contacted they described it as 0.8 MilliThe powder does convert into thin gel like sonsistency when dissolved in cold atrer (in contrast to LMW HA which does not form gel when mixed in water). Any help would be really appreciated. Thanks

    • drjohn says:

      High molecular weight (HMW) HA is always >1,000 kDa. Anything lower than that (10-1000 kDa) should be considered LMW. The powder granule size tells you nothing about MW. The bulk Supplements products is HMW in the sodium salt form.

  43. Jocelyn says:

    I know I’m late to the party here, but after reading this post last night I contacted Paula’s Choice because I’m another reader who has relied on PC to provide well formulated products based on science rather than industry hype. I have been using the PC hyaluronic acid booster for some time now (and it is fairly expensive so I want to know it’s doing some good). Here is their response to my inquiry:
    “Thank you for reaching out to us! I would be more than happy to help. Our RESIST Hyaluronic Acid Booster uses a combination of low molecular weight hyaluronic acid, high molecular weight hyaluronic acid and sodium hyaluronate for a cocktail approach to skin-identical ingredient and NMF (natural moisturizing factor). None of these ingredients is inflammatory when used topically and responsibly.
    Low molecular weight hyaluronic acid is capable of penetrating below skin’s surface, but not much deeper than that. Ingredients like antioxidants and skin-identical ingredients need to stay in skin’s upper layers to yield their intended benefits, including defense against environmental free-radical damage (which hits the skin’s surface first).”

    So, yes, I’m disappointed that she does in fact use LMW HA in her product(s). What percentage of the HA used is LMW is unknown, of course. I have a freshly new bottle I’ve just begun using and I’m now on the fence as to whether I should continue using it. At $45 for just 0.67oz I’m inclined to finish it up before moving on to the Timeless serum suggested above. What to do! At any rate, I’m just a lay person who likes to stay informed and spend my limited resources on things that work well, and very much appreciate the solid info shared here. Cheers!

    • drjohn says:

      I understand PC has a staff of “researchers” but not actual PhD or MD level scientists. I think they have the best of intentions, but don’t always get it right in the deeper aspects of the science. We respect them for their adherence to quality standards, nonetheless. Why don’t you send them a list of the key reference we provide here, and ask them for a response? Maybe you will tickle their interest to read further on the subject.

  44. Martha Landon says:

    I’ve really enjoyed reading your site and have learned so much. Have you all taken a look at the new-ish Skinmedica HA5 product? After seeing that you felt like the The Original Hyaluronic Acid Serum 100% Pure 2 oz. from Timeless Skin Care on Amazon for $9.98 was a great deal and works well. The SkinMedica HA5 is $178.00 on their website. Wondering what theirs has to offer that the Timeless version is lacking? Thank you for any thoughts.

    • drjohn says:

      I find HA5 to be both confusing and disturbing. It’s marketing message is that it contains 5 different forms of HA. 1. cross-linked HA, 2. non cross-linked HA 3. sodium HA 4. time release HA, and 5. nano HA. The latter sounds like HA hydrolyzed into LMW fragments, since intact HA molecular size is more than 3,000 nm.

      You can read here and look up all the references as to why we think LMNW HA has major problems in causing inflammation and inhibiting healthy, non-scarring matrix production. As to #4, why would time release HA be of value (other than a marketing gimmick?) Released from what? There is much confusion out there about the difference between sodium hyaluronate and HA. This just adds to it. The sodium salt is the exact same HA molecule, but in order to create the salt the native form may become purified of other tagalong molecules that like to attach to HA. Those might be lipids, or even growth factors. Of course with synthetic HA you start with a pure salt of some sort anyway (could be K+ or whatever). The notion that it is smaller and therefore penetrates skin better is not accurate. Even the Na+ salt is a huge molecule and not likely to gain entry in any meaningful numbers.

      Now we like topical cross-linked HA for several reasons, most especially because it forms a stable framework in which we can embed some of our favorite growth factors and anti-inflammatory cytokines. But there is no attempt here to take advantage of this. Instead, they add some non-science (quackish) ingredients like plant stem cell extract. Any company that does that is showing its true colors – short on science, the marketers have taken over, there is a sucker born every minute, etc. Sad, because a few years ago SkinMedica was a thought leader and did good quality science. I hope for the sake of the consumer they get back to their medical roots.

  45. Clementine says:

    Hi drjohn,
    Wow, I can’t believe I found you! You appear to be the HA guru and then some!
    At any rate, thanks for all the well researched data and advice. The following quote from you last year reads this:
    “Getting them all and using them will break the bank and eat up half your day, so look for products that contain multiple actives. Your BFT hosts, drjohn and drgeorge, developed one you may want to consider that we think is best in breed. Email us if you want to learn more about it.”
    Yes, I would like to know more about this. Is it available yet?

    Also, in another reply to a reader you said this: “….. put together a product combining HA with KGF for vaginal rejuvenation (also for vulva). We call if RejuVV, currently in clinical testing.”

    Is RejuVV available yet and in its absence do you still recommend Hyalofemme on Amazon?

    Finally and in relation to VA do you recommend the High Molecular Weight oral capsules and if so, any brand in particular you would recommend?

    Many thanks for your insights and time and sharing your knowledge with we laypeople.

    • drjohn says:

      Not so sure about oral HA for VA. No evidence I know of. Once HA gets to the gut it gets digested, hydrolysed, broken down to peptides and amino acids. Then it takes a first pass through the liver where it gets shunted into all sorts of pathways. best way to get some surface action going intra-V would be more direct application. Hyalofemme fits the bill. Wish it were free of other chemicals though. You could buy HA in bulk and make your own (until we get RejuVV out there).

  46. David Archer says:

    Hello Doctor,

    So I recently had an eye exam and it turns out I have a little dermatitis around my eyelids. My Optometrist recommended a HA-based eyelid soothing cream called ilast, which is 0.5% Sodium Hyaluronate. Do you have any thoughts on the ilast product line? There is ilast clean and ilast care. Both are HA-based, but the clean is 0.2% Sodium Hyaluronate, and the care is 0.5% Sodium Hyaluronate. This is the HMW HA correct?

  47. Lily says:

    Hi Doctor,

    How do you feel about the Ordinay’s hyaluronic acid + B5 serum based off the ingredient list? The description states it contains LMW HA. Should I discontinue use of the serum?

    http://ordinaries.com/product/rdn-hyaluronic-acid-2pct-b5-30ml

    Here are the ingredient provided:
    Ingredients
    Aqua (Water), Sodium Hyaluronate, Sodium Hyaluronate Crosspolymer, Panthenol, Ahnfeltia Concinna Extract, Glycerin, Pentylene Glycol, Propanediol, Polyacrylate Crosspolymer-6, PPG-26-Buteth-26, PEG-40 Hydrogenated Castor Oil, Trisodium Ethylenediamine Disuccinate, Citric Acid, Ethoxydiglycol, Caprylyl Glycol, Hexylene Glycol, Ethylhexylglycerin, Phenoxyethanol, Chlorphenesin.

    • drjohn says:

      Lily, looks like another product where the “formulators” (or maybe just marketers) ignore the compelling published, peer-reviewed medical evidence base – how expedient. Web site rather telling -products about fashion, not about science.

  48. JAS says:

    what are your thoughts of a product based on both HMW & LMW-HA in an ratio favouring HMW-HA, so to give the potential benefits of both types?

    • drjohn says:

      Makes no sense since there is no clinical benefit to LMW-HA, as indeed many studies show that small fragments down regulate regenerative process and act as inflammatory stimuli.

  49. C says:

    Oh how I have enjoyed reading this! Thank you so much!

    May I ask one thing, which remained unclear to me – does HMW HA prevent certain active ingredients from penetrating deeper into the skin? If it acts as a barrier to lock moisture in, does it lock other things out?

    I am wondering about vitamins and the like applied in form of an oil on top of an HA serum.

    Looking forward to your answer, will be highly appreciated.

    • drjohn says:

      Good question! There are a group of proteins that bind to HA (hyaladherins). Some of this are cytokine/GF signaling molecules which can be active ingredients (e.g. present as constituents of conditioned media of stem cells). This does not, however, mean that HA locks these actives out – in fact it may provide them with a safe harbor so that they can be released by diffusion and amplify an effect, or prolongs its action. We think of HA sometimes as being a molecular chaperone. Especially in the context of microneedling, where the skin barrier is penetrated. For other (non-hyaladherin) actives, providing an HA protective layer helps prevent degradation of e.g. delicate proteins by keeping them moist and in contact with stratum corneum. It makes more sense then to use HA as the top layer. As a glycoprotein, mixing oil in confuses the picture.

  50. Leuca says:

    I kept reading about this LMW HA craze so I simply googled it and yours was the first page that came up. Based on how companies tend to label their products vs what ingredient manufacturers are telling them, is there really a safe way for people to decipher ingredient lists anymore, at least when it comes to ingredients such as HA? I see companies like Paula’s Choice/Drunk Elephant stick to HA/SH/SHCP on their ingredient lists; what is the chance that said ingredients could actually be hydrolized and there is a miscommunication?

    After a recent bout of contact dermatitis from a bunch of bug bites, and as somebody who tries to be up-to-date in taking care of my skin in general, I’m scared that I could be inadvertently purchasing a product that could be not only slowing my recovery, but hurting my skin’s long-term health/appearance in the process.

    • drjohn says:

      Leuca, we appreciate your concerns. Because the use of LMW HA is scientifically unsound and therefore mostly used as a marketing trick (“our HA is better than their HA”) then I would suspect that if they are employing it they are also putting it on the label and advertising it as such. And because it takes an extra step to make it LMW, it adds a bit to the cost. So I wouldn’t worry about that. But you are very wise to look into these things, because so much of what is marketed is so completely whacky and just as likely to do harm than good.

  51. Shelly says:

    Hello Doctor – Thanks so much for your wealth of information and sharing it with us!
    Could you let me know the best order of applying products for am/pm facial care. For am – wash, tone, serums (vit.C, Coenzyme Q10, etc…) HA serum, moisturizer and then sunscreen. For pm – wash, tone, retin A, HA serum, moisturizer. I question when to apply the HA serum. Thanks again!

    • drjohn says:

      HA stays on the surface, doesn’t normally penetrate intact skin, and helps construct the natural defense barrier against the ravages of the world. HA should be the topcoat.

  52. MishyMash says:

    Great article – the information and humor are greatly appreciated! I reserve the ULMW HA (5k daltons or less) for formulations containing actives, such as LAA and peptides, due to the clinical findings available via https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970829/. Junk science. clever marketing, or both????

  53. Rita says:

    Hi, I am looking into purchasing Pure Bulk Hyaluronic Acid (Bovine Sourced). It says it is long chain. I know you mentioned in your post that long chain is HMW HA. So, with that being said, do I just trust that this product HMW HA is high enough, and that it is not a MMW HA. I want to be 100% sure of what I am putting on my skin, so that I do not cause any harm to my body. The website does state that it is 1.29 x 10 da. I’ve tried to figure this out on my own, but I’m at a loss and would really appreciate your help if you don’t mind. Thank you

    • drjohn says:

      Looks like the HMW stuff to me. What concentration, and how will you use it?

      • Rita says:

        I would be mixing a 1% solution (HA and water) for my face.
        My mom is considering taking it internally due to the fact that her optometrist told her that the gel behind her eye was diminishing and that is why she is seeing “cob webs”. I know in your post you stated that most of the HA, taken internally, is excreted through the urine. Is it safe to put HA directly into the eye if it is diluted in a solution? And if so, do you have any recommendations on a solution that I could mix for her?

        • drgeorge says:

          Rita, we don’t understand. Are you asking whether a solution of HA placed directly onto the eyeball will be of benefit? If so, it seems very unlikely insofar as the HA withing the vitreous humor of the eye is there as a result of physiologic cellular processes that manufacture it locally within the posterior chamber of the eye. We are not ophthalmologists but the concept of placing HUGE molecules (HA is polymerized in solution with lots of water) topically on the globe of the eye and expecting it to migrate into the interior of the eye just makes no physiologic sense. I would suspect that natural tear formation will eventually wash the HA out of the eye. The result of what you are describing sounds similar to “artificial tears”.

  54. Diane says:

    Hello,

    After going through your article and comments, I think I need to stop using a product called Collagen Replenish Powder with HA & Vit. C by Reserveage Nutrition. I have been faithfully using this product since February of this year, once per day, a scoop of 2.6 grams, which is their recommended serving. (It’s in a powder form and I put it in my tea.) I contacted the company yesterday to ask which form of HA they use and this is copied and pasted from their reply back to me.

    “In regards to your question on Collagen Replenish- We use low molecular weight sodium Hyaluronate for Hyaluronic Acid.”

    I apologize if you have to repeat yourself, but is this junk and should I stop taking the product immediately and toss it in the trash? You may not be able to or can not answer the next two questions and I understand if you can’t. How long do you think it will take to get out of my system and do you think I caused any inflammatory damage in the meantime? I have been feeling ok really no different since I have been taking it.

    Thank you very much for publishing this article. How I came to investigating the form of HA is another story but your article is an eye-opener, just another reason to do the research first before ingesting any kind of supplement.

    Thanks again.

    • drjohn says:

      Yes, it is fragmented HA and thus should be avoided. LMW HA acts as an inflammatory biosignal. Opposite of what you want to hydrate, nourish, or replenish skin.

  55. Kim says:

    Hello doctors,

    This is a follow up comment to one I left a couple of months back re: the Timeless Skin Care HA prep you endorsed in an earlier comment. Did you see it? I had written to this company and asked them about the molecular weight of their HA; they replied that they currently used a medium weight, I believe I also cut and pasted some of their email in my comment. I think it wise to keep your readership informed of things like this, so they might buy wisely.

  56. Veronika says:

    Hello, I too have reached out to Timeless and they told me that they use medium weight HA in their serums and LMW in their sprays.
    I am considering purchasing the Hydraplenish Hyaluronic Acid Serum from Nature’s Way. They specifically list HMW HA on their ingredients list and Amazon reviews of this products are rated as high quality (by the fakespot.com website).

  57. Geraldine says:

    Hi
    Thanks so much for providing this wealth of information- greatly appreciated

    I make my own HA serum using HMW-HA. I have been applying it morning and night on my damp skin then I’ll mix a few drops of therapeutic grade essential oils (frankincense & geranium) to some Rose (or Jojoba oil) and moisturise my face/neck with that.
    Is it ok in that order or should I use the HA last?

    Lastly my recipe for the serum is very basic: distilled water, HA and glycerin and this is meant to last 2 weeks if kept refrigerated. Does that sound about right to you? Thanks in advance

  58. Ellie says:

    So in simple terms HMW good LMW bad? I recently purchased 100% Pure HA from Jaba Labs and after reading this article I went back and checked. It is Low. I have used it on 2 clients for Micro Needling. Should I be worried for them? I also sent some home with them to use for the rest of the day. Is there anything I can do with this product or should I just throw it out. I also purchased for myself their HA with Collagen and Vit C. Should I stop using it?
    On Amazon I have seen Pure Hyaluronic Acid Serum Powder (High Molecular Weight Sodium Hyaluronate). Cosmetic Grade,… Is this something I can just mix with water and use in my micro needle treatments. Thank you so much for all your help. 🙂

    • drjohn says:

      LMW is only good if you actually want inflammation. Let’s say you are trying to treat an open leg ulcer on a diabetic, or maybe grow hair. But for purposes of facial skin rejuvenation for aesthetic purposes, it makes no sense to add in an inflammatory agent which is counter to what you are trying to achieve. So yes, use HMW HA. As far as microneedling goes, follow the rule of “nothing other than native human molecules” at the time of needling, and for at least 4 hours afterward, to prevent foreign body or allergic reactions. So you have to read the label of any product. Even vitamin C has been associated with allergic granulomas. If you mix your own HA, make sure it is pure and comes from a reliable source. Use purified water, best to use sterile containers and utensils. You can greatly boost the effects of HA by adding native human biosignals such as growth factors. But these are not DIY molecules – they are highly specialized, so obtain through reliable channels.

  59. Ellie says:

    I am having trouble finding HMW HA. Do yo know where I can buy it?

    • drjohn says:

      I have made several recommendations only to find out later that they are products with problems. How about if Cellese just creates a simple, pure HMW-HA solution?

  60. imraan says:

    Hi Dr Jon
    I just wish to say that generally don’t reply to any sites but the information, the humour and the clarity of your explanations are fantastic. .take a bow!!!As a general practitioner it’s not my field but I do have an interest in aesthetics. I see a lot of patients in my clinic with Arv viz stavudine induced lipodystrophy of the face and was wondering if HA would help.this led me to doing some searching and I was lost till I came across this site.Really well written and you took the time to answer each question posed comprehensively.
    I hAve read above that it will FORM a barrier on the skin and HmwHa will not penetrative. My question is can it be injected and will that have any benefit at all.if so is the effect lasting or will it it succumb to enzymatic degradation at some point…I’m just shooting in the dark here as I am new to this.
    Again ,many thanks for all the detailed answers you have provided..it was really well worth the read
    Sincerely
    Regards
    Dr imraan essa

  61. Alex tosas says:

    Dr.john … Yes have cellese make the hmw ha please👍

  62. SandraP says:

    I came across this article a few days ago when doing some research on HA… thinking of mixing my own lil serum at home has turned into an unending list of questions (bovine or vegan, long chain or short chain, low molecular weight or high molecular weight, trusted or non trusted manufacturer). It’s taken me three days to come back to this article because one click led to another which led to another and on this site, every link is more interesting and informative than the last! I’ve only just breached the tip of the informational iceberg on your site and I can’t wait to read more. Thank you for putting out real, scientific opinions.

    My question references something that come up early on in this thread – you commented that you’re working on a HA mask… I’ve tried looking up Cellese and a mask, but see nothing. I also read above more recently that you’re realizing maybe you should offer a good grade HA for home use.

    Any more info on this mythical HA mask?! Any info would be greatly appreciated.

  63. Kika bjorkman says:

    Hi,
    What about Barbara Sturm hyluronic with long chain and short chain??
    Is this really that good?
    Thank you

    • drjohn says:

      Short chain HA is never good (unless for some reason you want to induce inflammation and suppress protein production).

  64. Kika says:

    Thank you for making it more clear. I suppose companies use short/long chain verbiage now to attract buyers, as it sounds like it packs more of an Antaging punch!

    • drjohn says:

      Yes Kika, sounds good … but the science says it is anything but good. There is a lot of creative “marketing” by folks who actually haven’t a clue what they are talking about.

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