Efficacy of different MWs of hyaluronic acids

LeoLeo Member
Need opinions on efficacy of the different MWs of HA for facial use. Which MW to use for which indications and at what dose range of use? 

Comments

  • MarkBroussardMarkBroussard Member, Professional Chemist
    The best performing HA is in the range 120 - 200 kDa ... it's a wound healing grade generally used at 0.2%.

    It all depends on what you want the HA to do:  Super Low MW HA will penetrate the dermis.  Higher MW HA forms a barrier film on the surface of the skin preventing TEWL.
    Chemist/Microbiologist formulating in the Organic & Naturals arena under ECOCert/Natural Products Assn/Whole Foods/National Organic Program guidelines focused skincare & haircare products. 

    See website for details www.desertinbloomcosmeticslab.com
  • HA soaks up water like a sponge.

    If HAs would indeed penetrate and have activity, it would soak up water from the dermis resulting in not much difference since the water is already in the dermis that it is soaking up?

    Why would the higher MWs form a barrier shield? I would think it would either not do anything if the barrier is intact or pull out and remove water from the skin as it sits on the top of the skin soaking it up from the epidermis/dermis and increasing TEWL?

    Please correct me if I am wrong....If the HAs are injected under the skin into the dermis at much high concentrations, then you get the visible effects that last for a few months or longer.




  • MarkBroussardMarkBroussard Member, Professional Chemist
    edited December 2020
    The HA in a cosmetic product such as a serum or cream is already fully-hydrated when applied to the skin, so its ability to draw water from the skin in deminimus, if at all. 

    Higher molecular weight HA, when applied to the skin, is too large to penetrate the dermis, and again, it is fully hydrated when applied to the skin.  As the water evaporates, it will form a barrier film.

    Super Low Molecular Weight HA can penetrate the dermis, but again, it is fully hydrated when applied to the skin in a cosmetic product.

    So, the question you must ask yourself if your hypothesis is true is:  How does fully-hydrated HA absorb or draw water from the skin when it is at it's maximum capacity of hydration when applied to the skin? ... It won't. 
    Chemist/Microbiologist formulating in the Organic & Naturals arena under ECOCert/Natural Products Assn/Whole Foods/National Organic Program guidelines focused skincare & haircare products. 

    See website for details www.desertinbloomcosmeticslab.com
  • chemicalmattchemicalmatt Member, Professional Chemist
    I can add that the higher MW HYA allows your skin to feel as supple and elastic as a newborn's.  Lower MW? - not so much.
  • I can add that the higher MW HYA allows your skin to feel as supple and elastic as a newborn's.  Lower MW? - not so much.
    Can you give me a Dalton range for high MW that you've had that good experience with? I have 800,000 - 1,000,000 Daltons but now that I read your comment I'm wondering if I should get the 1,000,000 - 1,500,000 Daltons.
  • chemicalmattchemicalmatt Member, Professional Chemist
    Emma, that one you have will do fine in nearly any application. The lower MW ones trend to the 500,000 Dalton range.
  • Many higher-end, top-quality facial skin products use multiple types of hyaluronic acid.  I do believe that at least one published study found that very low molecular weight hyaluronic acid is pro inflammatory, so for the moment, I am steering clear.  I do wonder how these components differ in their function from humectants, such as glycerin, which also purportedly draw water to the skin.

  • suswang8 said:
    Many higher-end, top-quality facial skin products use multiple types of hyaluronic acid.  I do believe that at least one published study found that very low molecular weight hyaluronic acid is pro inflammatory, so for the moment, I am steering clear.  I do wonder how these components differ in their function from humectants, such as glycerin, which also purportedly draw water to the skin.

    Due to the liberties granted to us on the INCI (Below 1% liberties).... Unless you work for those companies,...you have NO IDEA how little HA they are using.  I think they are using tiny amounts as a 'claim' ingredient.  IMO, there are better humectants.  Mark has a VERY valid point...about HA already being fully hydrated before it even touches your skin.  In full disclosure...I use HA in all but one product, and I view it as 'label appeal'.

  • MarkBroussardMarkBroussard Member, Professional Chemist
    edited December 2020
    I'm currently working wound healing products for a couple of different clients.  Pro-Inflammatory is not necessarily a bad thing, it all depends what effect you are trying to achieve.  You might find this interesting reading:

    https://www.woundsresearch.com/article/hyaluronic-acid-inflammation-and-tissue-regeneration
    Chemist/Microbiologist formulating in the Organic & Naturals arena under ECOCert/Natural Products Assn/Whole Foods/National Organic Program guidelines focused skincare & haircare products. 

    See website for details www.desertinbloomcosmeticslab.com
  • Everyone has good opinions but no one knows for sure if the HAs are doing anything at all when applied to skin as opposed to injections. Are the HAs only soluble in water?
  • Has anyone tried to formulate the HAs in an anhydrous formulation or deliver the HAs in a powder form? Any unique delivery systems been tried?
  • Normally HAs are water soluble, you might want to look for the oil soluble or dispersible or ones with different "delivery" systems on ulprospector. 
  • @jermolian Do you or anyone on this thread have any suggestions for different delivery systems for the anhydrous HAs?
  • MarkBroussardMarkBroussard Member, Professional Chemist
    Leo said:
    Everyone has good opinions but no one knows for sure if the HAs are doing anything at all when applied to skin as opposed to injections. Are the HAs only soluble in water?
    Seriously? ... this falls in the category of Fake News.

    HA is water-soluble, there are a couple of HA dispersions in oil, but HA is not oil-soluble.

     https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970829/#:~:text=Conclusion: The new nano-hyaluronic,the end of eight weeks.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583886/


    Chemist/Microbiologist formulating in the Organic & Naturals arena under ECOCert/Natural Products Assn/Whole Foods/National Organic Program guidelines focused skincare & haircare products. 

    See website for details www.desertinbloomcosmeticslab.com
  • @MarkBroussard. Mark, I am not here to argue with your beliefs. One day you will realize the truth. The studies that you are sending me on your links have major limitations, are flawed and are not able to be reproduced.

    With regards to the 1st link, the investigators used a specialized so-called nano-HA (not the typical HAs that you can purchase) which is not readily available to confirm the results and its a quantum leap to believe that all HAs are alike or will behave similarly. Yes--they did a study to show that their nano product showed some efficacy but do the data and the stats and the results have merit? You have do your own analyses to decide.

    The 2nd point is that they did NOT do a double blinded randomized placebo-controlled study or a paired comparison to see if one side of the face performed better than the other. These are weakly designed studies usually done to get a quick answer with gamed stats for a company to market their proprietary product.

    The 3rd point is that the article uses gamed statistics to come to their conclusions. By gamed stats, I mean percentages. The use of Percentage reductions are gaming stats that carry very little weight when used in studies with small numbers of subjects. If I improve my wrinkles from a 1mm to a 2 mm depth, I am improving 100% for that 1mm change. Is this really important and does it have any significance? The 1mm change can be at their limits of sensitivity for detection and impacts significance conclusions due to huge standard deviations with large errors. For these stats to be of any significance, you need over 100 people in the study not just 33.

    The 4th point is the study was published in an obscure journal that needs articles to publish or perish. If I were a reviewer, I would not have accepted it for publication.

    I could go on and on and on.
    The study is interesting as a preliminary observation but not very valuable to make generalizations of true HA efficacy.

    With regards to the 2nd link, it is a review and reviewers can write whatever opinions they want to write and conclude whatever they like to conclude since it is not a study and they may be referencing similar poor studies.

    I am not convinced that HAs have any added value (other than marketing) when provided as topical agents beyond that of any moisturizing ingredient since NO validity exists.

    It is not me that is providing fake news. There is a huge contamination of science with fake news from studies that are highly lacking in scientific rigor and integrity.

    Science is great and science is the ultimate truth but science is highly contaminated with fake science! 

    Over 95% of the published scientific work is fake news from industry....

    In the cosmetic world, marketing rules and scientific truth is even much much and extremely harder to find. Fake news is rampant in the cosmetic world and we are the sheep that believe it! It makes us feel good to believe it so we just accept it without question just like sheep....
  • MarkBroussardMarkBroussard Member, Professional Chemist
    edited December 2020

    "Over 95% of the published scientific work is fake news from industry...."

    Those are only two from a multitude of studies on Hyaluronic Acid ... If this is your belief system, that virtually everything published in scientific journals is fake news from industry ... then your position is that you can believe almost nothing.    
    Chemist/Microbiologist formulating in the Organic & Naturals arena under ECOCert/Natural Products Assn/Whole Foods/National Organic Program guidelines focused skincare & haircare products. 

    See website for details www.desertinbloomcosmeticslab.com
  • Yes---It is my belief system that the majority of published ingredient studies in the cosmetic literature on wrinkles/facial imperfections are not reproducible or efficacious in real life. The majority of the studies on topical HAs are PR marketing briefs (not rigorous studies) from ingredient companies published in inferior journals that exist to publish inferior studies or perish.

    I keep an open mind and put the ingredient of interest to the test and see for myself....I search for my truth....by performing my own pilot clinical studies. If the ingredient is truly active, it should provide a visible effect that is noticeable.

    Subjects use the HA product by itself, in a vehicle containing only one or two ingredients max, on one side of the face and only the vehicle on the other side of the face. If the subject and I can see a visible WOW result when comparing the 2 sides (weekly after 8-12 weeks of use), it works. If not, its fake news.

    I have the luxury of seeking and finding the truth and not propagating the fake marketing news from others.

    50 years ago, clinical studies were not heavily contaminated with fake stats by industry statisticians. Now--Contamination by industry is the norm. My professor at a major university once told me: Numbers do not lie but All Statisticians distort the numbers to show efficacy...which is very easy to do today with the use of the right stats programs. 

    He also taught me:
    1. Seek the truth for myself
    2. Keep an open mind
    3. Be skeptical
    4. Do not quote/spread fake news (verify it in real life yourself)

     I do not want you to think that I am hard headed or untrustworthy of others. I am a critical thinker and I appreciate well designed and carried out studies that have been shown to be reproduced by other groups of investigators not tied to industry (with stats that I can analyze and verify to be robust).



  • What makes HA fancier than its cousin xanthan gum? Wasn't xanthan gum also used for intra-articular injection and doing good? Why no cosmetic company doing research and making interesting derivatives and selling-points out of xanthan gum?


  • MarkBroussardMarkBroussard Member, Professional Chemist
    @Leo:

    If you are able to conduct your own "clinical studies" on your cosmetic concoctions validated by an eyeball analysis ... good for you.  But, that is not necessarily a pracitcal approach for most practitioners in the field of cosmetic ingredient/product development ... if you feel the need to verify everything for yourself as opposed to relying on published studies, again, if you have the capability, good for you.  But, again, that is simply not practical for most.

    Many studies on cosmetic ingredients are sponsored by ingredient suppliers as a simple matter of economics ... what is the value of the time/expense of studying a particular ingredient and what analysis/study is sufficient to prove some level of efficacy? 

    As there are very few proprietary molecules in cosmetic science, it is simply not economic to conduct large scale clinical studies on any one particular ingredient that is not patent-protected, particulary if there are multiple suppliers of that particular ingredient and no one company has a proprietary, protected position on the ingredient or ingredient combination.  Unless the research is conducted by an industry consortium or if it's pure academic research and the government pays for it (someone has to pay for it), the research simply will not get done if some party does not have a vested interest in the study and economics of the ingredient.

    The question is:  what information is worth what level of investment to become known?  Cosmetic scientists are not curing disease ... simply trying to improve skin appearance and reduce wrinkles ... so when you put the objective in context and balance that out with the capital investment required to obtain the data/information, well, the parties with a vested interest, the ingredient suppliers. fund quite a few of the studies for ingredients they manufacture.  That does not necessarily mean that the researchers they funded to conduct the studies are fabricating the data & information.

    "Numbers don't lie, but liars can count" ... sure, there may be some of that.  Again, no reason to not trust published cosmetic chemistry studies at all.

    I am currently working on two separate product lines each of which employ patented, proprietary molecules so the type of studies you are describing are appropriate since there is a patent-protected molecule in the formulations.  But, for another HA serum, that does not make practical/economic sense, so you rely on whatever published research is available.
       
    Chemist/Microbiologist formulating in the Organic & Naturals arena under ECOCert/Natural Products Assn/Whole Foods/National Organic Program guidelines focused skincare & haircare products. 

    See website for details www.desertinbloomcosmeticslab.com
  • LeoLeo Member
    edited December 2020
    I am only questioning the efficacy of any topical product that makes claims to affect anti-aging wrinkles. Its hope in a bottle. 

    Without some form of irritation, as seen with retinoic acid and retinol at the concentration that causes the irritation, I have not seen any topical ingredient have any effect....and I have tested 100s and it is easy to visibly prove with a paired comparison with the vehicle.

    I have a graveyard of 100s of ingredients that do not perform....but there are a few that have promise but they cause irritation for the effect.
  • PerryPerry Administrator, Professional Chemist
    @Leo ; and @MarkBroussard - great discussion! I appreciate both perspectives. It is very difficult in cosmetic science to discover something that is "real" and not just marketing hype from an ingredient supplier or cosmetic manufacturer.

    I tend to find @Leo's position more in line with my own, although I'm not quite as cynical. I agree with @MarkBroussard and don't think studies published in journals are "fake" or made up. I believe the data is real & the scientists who do the studies are mostly sincere.

    But there is certainly a positive bias. No raw material company is going to publish a study which proves their ingredient has no benefit. This file-drawer effect is found throughout science, but it is particularly strong in cosmetic science where companies are conducting studies to support specific outcomes. 

    One other thing worth pointing out is that consumers are terrible at detecting differences, especially differences over time. They are easily influenced with stories and packaging and pricing. The fact that a dermatologist saw some benefit over 8 weeks or a lab measurement showed a statistical difference matters little if the consumer doesn't notice. If you can match the aesthetics, it would make more economical sense to create a formula using Glycerin with a splash of Hyaluronic Acid. You get the same story at a fraction of the cost & consumers won't notice anyway.
  • MarkBroussardMarkBroussard Member, Professional Chemist
    @Perry:

    Yes, of course there is a positive bias in published research. 

    It's again a matter of the economics and the value of time ... unless your "negative result" research disproves something that was either generally accepted to be true and/or indicated to be true through prior published research, then your "negative or null result" research has no value to anyone.  Who is going to spend the time writing, reviewing and reading a research paper that does not yield valuable information that you can do something with on a proactive basis?  There is no point in the exercise.

    Ditto ... yes, ultimately it's the consumer who determines the value of skin care products by either purchasing or not purchasing those products.  
    Chemist/Microbiologist formulating in the Organic & Naturals arena under ECOCert/Natural Products Assn/Whole Foods/National Organic Program guidelines focused skincare & haircare products. 

    See website for details www.desertinbloomcosmeticslab.com
  • @Perry. Does HA mix well with glycerin? What other agents will mix with the HAs that contain no water?
  • Lower MW have better penetration
  • @Leo
    You have to use water.
  • PattsiPattsi Member
    edited December 2020
    Leo said:
    Has anyone tried to formulate the HAs in an anhydrous formulation or deliver the HAs in a powder form? Any unique delivery systems been tried?
    Leo said:
    @Perry. Does HA mix well with glycerin? What other agents will mix with the HAs that contain no water?
    May I ask why do you not want to use water?
  • @Perry I do not follow the party line about HAs since I am skeptical until proof of adequate scientific quality is provided.

    I do not believe that topical HAs do anything other than sit on top of the SC and provide and/or accumulate water from either the product itself which contains water or the atmosphere.

    This may not be a good thing for healthy skin since it leads to a disruption of an SC barrier integrity. Why disrupt the SC barrier with water? Skin, like hair, needs oil and not water unless the intent is disrupt the natural oil-based barrier.

    I have a different idea--to use the HAs to grab water from the atmosphere and have the HAs remove water before it disrupts the barrier--use HAs as a protectant from water--so why would I want to provide water with a HA ingredient that has been saturated with water? Once HAs are saturated with water, they are more harmful than good--unless your intent is to damage the natural barrier.

    If you believe that the HAs penetrate the SC barrier and bring with it water, which I do not, and HAs enter the dermis, which I do not, then the HAs would go into the skin fully saturated with water, damage the barrier and produce leaky skin followed by a cascade of water-infused events with water going in and out of the skin affecting permeability.

    However, it is my view that HAs only function from outside the skin by grabbing water and not allowing atmospheric water to harm the SC --if not already fully saturated with water.

    So-- why add water to a HA formulation. It defeats the purpose of its purported activity!


  • I do not believe that topical HAs do anything other than sit on top of the SC and provide and/or accumulate water from either the product itself which contains water or the atmosphere.

    This may not be a good thing for healthy skin since it leads to a disruption of an SC barrier integrity. Why disrupt the SC barrier with water? Skin, like hair, needs oil and not water unless the intent is disrupt the natural oil-based barrier.

    I have a different idea--to use the HAs to grab water from the atmosphere and have the HAs remove water before it disrupts the barrier--use HAs as a protectant from water--so why would I want to provide water with a HA ingredient that has been saturated with water? Once HAs are saturated with water, they are more harmful than good--unless your intent is to damage the natural barrier.

    If you believe that the HAs penetrate the SC barrier and bring with it water, which I do not, and HAs enter the dermis, which I do not, then the HAs would go into the skin fully saturated with water, damage the barrier and produce leaky skin followed by a cascade of water-infused events with water going in and out of the skin affecting permeability.

    However, it is my view that HAs only function from outside the skin by grabbing water and not allowing atmospheric water to harm the SC --if not already fully saturated with water.

    So-- why add water to a HA formulation. It defeats the purpose of its purported activity!

    Then Glycerin and other water-soluble molecule is damaging the SC barrier too? This make me concerned.


  • Glycerin and HAs do not damage the SC barrier since they are not absorbed unless the SC barrier is disrupted. They sit on top of the skin and grab water from the atmosphere like a sponge and keep the SC barrier intact. If they occlude the barrier, they may prevent TEWL. I think of them as protectants from the damaging effects of water on the SC. I fail to understand all the marketing hype around the HAs....no better than glycerin.

    Look, every 10-20 years, the marketers come up with an idea to make certain that cheap and effective ingredients get a bad rap so they can introduce expensive ingredients with sexy unproven science. We did this with mineral oil, petrolatum, silicones, etc., and the list gets larger--the marketers and ingredient companies have to make a living --right? We just follow the party line and formulate their expensive sexy unproven stuff like good soldiers. These days, it is all about the story and not whether it works or not or whether it is any better than the old stuff....


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