- It’s naturally in our skin and behaves there like a sponge
- It can bind up to 1000 times its own weight in water
- Awesome moisturizer and has other important biological functions
- Different molecular weight versions exist and that raises questions
- Skin penetration abilities of high-molecular-weight HA is debated (see geeky details for more info)
- Usefulness of low-molecular-weight HA is also debated (see geeky details for more info)
Hyaluronic acid (HA) and its various forms are the current IT-moisturizers. In this case, the fame and hype are pretty well deserved, however, there are some debates and question marks around it.
So let’s see, what is hyaluronic acid and even more importantly what’s the big deal about it?
HA is a nice big sugar molecule (more precisely a so-called glycosaminoglycan, or GAG) that can be found naturally in our body. It’s the most dominant, and most important molecule in the liquidy stuff between our skin cells (sciency name for it is extracellular matrix or ECM). A 70 kg adult has about 15 g of HA in her body, and half of it is in the skin. Most of the skin HA is in the dermis (the deeper layer - about 0.5 mg/kg) but there is also some in the epidermis (the upper layer - about 0.1 mg/kg).
Saying it’s a big molecule, doesn’t do it justice. By default, it’s a HUGE molecule. Its molecular weight can be up to 4 million Danton (that is just the unit molecular weight is measured in). To compare, normal table sugar that you bake with has a molecular weight of 340 Dalton.
Actually, this whole molecular weight thing is super important and it’s the basic source of debate and questions. There are two main categories:
- High molecular weight HA, or HMW-HA: there is not a super clear definition but in the range of 0.5-4 million Danton, let’s say it’s a HMW-HA.
- Low molecular weight HA, or LMW-HA: here again no super clear definition but one paper mentioned that they define it as HA whose molecular weight is below 300k Danton.
This molecular weight question is so very important because it seems that the different versions behave very much differently in our skin.
All about high-molecular-weight hyaluronic acid
Let’s start by discussing HMW-HA. First, you have to know that this is the version that can mostly be found by default in our skin. So what does it do?
It’s the sponge in our skin
HMW-HA has superstar water-binding abilities. It can bind 1000 times its own weight in water. Or to say it another way 1 gram of HA can bind up to 6 liters of water! That is a lot, and this makes HA pretty much the best water-binding ingredient we know today. It is really the sponge of our skin: it’s there in the outer layers and helps our skin immensely to attract and retain its water content.
It also has many other important biological functions
HMW-HA is far from being just a simple moisturizer. A 2012 and a 2015 research study summarizes what we know so far from this amazing huge molecule.
From the aspect of our skin and aging:
- it’s super important for healthy skin hydration and maintaining the elasticity of our skin
- it reduces inflammatory response in our skin
- it helps to regenerate damaged skin barrier
- it helps to reduce wrinkles that appear with age due to water loss
- it has great space-filling capacity, that also means it can plump up the skin and make it look younger
The next ones are not about our skin but just so you know it really has several important biological functions:
- it’s vital for the lubrication of our joints so that they can move easily and happily
- it gives the framework through wich cells migrate in our body (at wound healing or at certain immune responses our cells move)
- it can inhibit the growth of new blood vessels that is important in treating cancer
So HMW-HA seems to be a super nice thing for our body and for our skin. There is no question about that. However, there is a question about whether HMW-HA can penetrate the skin or not if you just smear it on via some nice serum or moisturizer. That is one of the big, and debated questions: Can HMW-HA penetrate the skin?
To answer this burning question it’s good to know that the skin is often imagined as a brick and mortar wall where the bricks are the skin cells and the mortar is the liquidy stuff between them, the extracellular matrix (ECM). And we know that for something to penetrate the skin it has to be small enough to fit between the skin cells. Also, skin prefers oily things to absorb rather that pure water or water-soluble things. HMW-HA is water soluble and huge. So of course, everyone in their right mind would think that it cannot penetrate and several experts do think that.
For example very famous and notable expert dermatologist, Leslie Baumann MD writes in her Cosmetic Dermatology textbook (which we are a huge fan of!) that HA cannot penetrate the skin and refers to a 1998 research about this (that unfortunately we could not find and read). Also, a very recent, 2016 article in the Journal of Drugs in Dermatology mentions (without a source though) that two things hinder HA being the "holy grail" of skin hydration: "total lack of penetration and rapid degradation of externally applied HA".
But don't despair, we also have some good news: even if HMW-HA cannot penetrate it still seems to be a great and useful ingredient on the surface of the skin. It can provide great surface hydration and it can form a protective barrier.
And further good news: A research paper done in 1999 has measured the absorption of HA on intact skin and has found that against all odds HA seems to penetrate into the skin! They have done the experiments both on mice and human skin and have determined that HA was absorbed both into the outer and the middle layer of the skin (epidermis and dermis). The researchers think that the reason for this is that HA is probably not going through the epidermis passively just by itself, but instead, the skin has some kind of active transport mechanism to help HA’s absorption.
So bottom line about HMW-HA (as a topical ingredient): At the minimum, it's a great surface hydrator. At the maximum, it's much more with an important role in keeping the skin healthy and plump.
Phewww, that was already long! But brace yourself, as HMW-HA is only half of the story.
All about low-molecular weight hyaluronic acid
LMW-HA is all the rage and hype nowadays so what about that? Well, we wish we could just simply confirm that it's awesome, it can penetrate better and deeper and it's the holy grail of hydrating the deeper layers of the skin.
But digging into the research around LMW-HA, it quickly turns out that the biological role of LMW-HA is crazy complicated, and it's not entirely clear if putting it all over your face is a good idea or not.
It's been understood for quite a while (we found a research already from 1986 about it) that LMW-HA plays a special role at sites of inflammation and tissue repair. It seems to be clear that if there is an injury the HMW-HA (that's in the skin by default) is broken down into small pieces and the small HA pieces play a complicated and important role in the wound healing process.
There are plenty of research papers trying to understand what happens at wound healing and the majority of the studies point in the direction that LMW-HA is kind of a bad guy and sets off pro-inflammatory responses in the body. A great research paper on HA from 2012 summarizes the role of LMW-HA like this: "smaller polymers of HA are distress signals and potent inducers of inflammation and angiogenesis".
But don't despair this is research about what happens in our body when big HA is broken down into small HA at a site of injury. It's not research about what happens to small HA when we put it all over our face. There is, for example, a 2008 study that found that LMW-HA increases the self-defense of the skin by inducing an antimicrobial peptide called β-Defensin 2. This same study also writes that "LMW-HA-induced activation of keratinocytes seems not to be accompanied by an inflammatory response, because no production of IL-8, TNF-α, IL-1β, or IL-6 was observed". (The little code names refer to small cell-signaling proteins involved usually in inflammation.)
What's more, we have also found a study (or rather two but it's by the same guys) that examined what happens to rosacea or facial seborrheic dermatitis (both inflammation-related skin diseases) patients when they use a 0.2% LMW-HA cream. And the patients did show an improvement and the authors theorized it might be because of the "immuno-normalizing effect" of LMW-HA.
The German manufacturer, Evonik also tried to examine if LMW-HA is pro-inflammatory or not when we smear it on. The studies "finding strongly suggests that HA with a molecular weight ≤ 20 kDa should not be applied whereas 50 kDa HA is safe". Evonik also did a Journal of Drugs in Dermatology published comparison of creams containing different molecular weight HAs and found that all formulas improved skin hydration and elasticity but the LMW-HA formulas were better at reducing wrinkles.
Well, there it is. We did tell you now the pros and cons, so if you feel LMW-HA is something you wanna use, it's probably ok, might be even great. If you are a "better safe than sorry" type, you might wanna stick to HMW-HA until research about the topical use of LMW-HA gets more solid.
Ok, that was really long and complicated, sorry for that. If you are still with us, congrats! You've just become a real HA-and-the-skin expert! :)
- Dermato-endocrinology, Jul 1, 2012, Hyaluronic acid: A key molecule in skin aging
- Journal of Drugs in Dermatology, January 2016, Rejuvenating Hydrator: Restoring Epidermal Hyaluronic Acid Homeostasis With Instant Benefits
- The Journal of investigative dermatology., 1999 Nov;113(5):740-6., Absorption of hyaluronan applied to the surface of intact skin.
- International Journal of Cosmetic Science, Volume 37 (4) – Aug 1, 2015, Stability determination of the formulations containing hyaluronic acid
- Journal of immunology, 2008 Aug 1, Low Molecular Weight Hyaluronic Acid Increases the Self-Defense of Skin Epithelium by Induction of β-Defensin 2 via TLR2 and TLR4
- SOFW Journal, 11-2008, M. Farwick, P. Lersch, G. Strutz (Evonik), Low Molecular Weight Hyaluronic Acid: Its Effects on Epidermal Gene Expression and Skin Ageing
- Journal of drugs in dermatology : JDD., 2011 Sep;10(9):990-1000., Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment.
- The Journal of clinical and aesthetic dermatology., 2012 Oct;5(10):20-3., Efficacy and safety of a low-molecular weight hyaluronic Acid topical gel in the treatment of facial seborrheic dermatitis.
- Journal of drugs in dermatology : JDD., June 2013 | Volume 12 | Issue 6, Efficacy and Tolerability of Low Molecular Weight Hyaluronic Acid Sodium Salt 0.2% Cream in Rosacea
- Journal of theoretical biology, 1986 Mar 21;119(2):219-34., A model for the role of hyaluronic acid and fibrin in the early events during the inflammatory response and wound healing.
- The Journal of clinical investigation., 1996 Nov 15;98(10):2403-13., Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages. The role of HA size and CD44
- American journal of respiratory cell and molecular biology, 2011 October, Hyaluronan fragments promote inflammation by down-regulating the anti-inflammatory A2a receptor
- Immunol Res. Author manuscript; available in PMC 2014 Jul 22., Tissue integrity signals communicated by high-molecular weight hyaluronan and the resolution of inflammation