Hyaluronic Acid for Skin Explained (25 Studies): EVERYTHING You Need to Know!

Sup, everyone? Today we will be discussing hyaluronic acid’s benefits for skin, and why molecular weight is important! As always, I will be going over the science and studies behind it in an easy-to-understand manner (or at least try). Product recommendations are at the bottom of this post.

Alrighty, let’s get you up to speed on everything you need to know!

What is Hyaluronic Acid?

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Hyaluronic acid (HA) is a naturally occurring glycosaminoglycans found throughout the body’s connective tissue. (1) Glycosaminoglycans are simply long unbranched carbohydrates, or sugars, called polysaccharides.

HA is the main component of the extracellular matrix, or uh… the thing that holds cells together to form living tissue like skin. (2) It gives your skin structure, is responsible for that plump-hydrated looking effect, plays a pivotal role in the wound healing process, and decreases as we age making us more susceptible to sagging and wrinkles. (3, 4)

Hyaluronic Acid Benefits.

For starters, it can bind up to 1000 times its weight in water! That’s one of the main reasons it’s used in skincare — in other words, it functions as a humectant, and holds water molecules onto the surface of your skin to keep it nice and hydrated.

Anytime we are talking about skin that is well moisturized, we’re mainly referring to skin that has a lot of water content. Perhaps you’ve heard of the term transepidermal water loss, or TEWL for short? This is the scientific term for the measurement of how much water is evaporated from skin.

When a product prevents TEWL, that means it is keeping your skin hydrated by making sure that water doesn’t escape from its surface. Hyaluronic acid does exactly that, i.e. slows the rate at which water evaporating.

Apart from being a very effective hydrator, a couple of studies have shown that it is very good for healing wounds! (5) Let’s break them down:

• A study on 50 patients with venous leg ulcers (view google images with caution O_O), found that applying gauze pads with 4 grams of 0.05% sodium hyaluronate cream for 21 days significantly reduced the severity of swelling (p < 0.001) and skin oozing ( p < 0.001). It also helped decrease erythema (redness), pain, and necrosis (premature cell death). (6)
• 11 patients with burn injuries applied 1.5% HA every day, and the study found it actually slowed down wound healing compared to just pure glycerin. (7) Yikes! This may have been because of the concentration and molecular weight of hyaluronic acid. More about this in the next section!
• A study with 152 patients found that applying 0.2% hyaluronic acid cream twice daily helped heal wounds from radiation therapy. (8)
• A hyaluronic sheet (sheet masks anyone? :p) applied once daily significantly reduced the healing time (p = 0.0003) of ulcers caused by venous insufficiency or vasculitis in 10 patients. (5) In other words, it helped heal ulcers that had inflamed or compromised blood vessels.
• 111 adult patients (age 18-75 years) with second degree burns, were asked to apply 0.2% hyaluronic acid + 1% silver sulfadiazine cream or 1% silver sulfadiazine cream alone for 4 weeks max. Both treatments were effective and all wounds were healed, but the hyaluronic acid cream group had a significantly shorter healing time (p = 0.0073). (9)
• A similar study to the one above was conducted and found the same thing. That is, silver sulfadiazine plus hyaluronic acid heals wounds a lot faster than silver sulfadiazine alone. (10)

And lastly, hyaluronic acid increases skin elasticity, (11) has been used to treat eczema (12, 13, 14), facial rosacea, (15) and reduces the appearance of wrinkles. (16, 17)

Hyaluronic Acid Molecular Weight. Why it’s IMPORTANT!

So it turns out that not all hyaluronic acid is treated equal. (11) There are some varieties that are a bit controversial, and increased levels of HA are actually linked to inflammatory skin diseases like psoriasis. (18, 19) Say waaaaat? 😮

Let’s discuss.

What hyaluronic acid is beneficial for skin has to do with its molecular weight and concentration. The molecular weight refers to its mass, or how big the HA molecule is. This is measured in something called unified atomic mass units, or dalton for short.

For reference, here are the various molecular weights of hyaluronic acid according to LotionCrafter (a cosmeceutical supplier):

• High molecular weight (HMW) HA = 1.0 – 1.5 Million Daltons (1000 – 1,500 kDa)
• Low molecular weight (LMW) HA = 0.8 – 1.0 Million Daltons (800 – 1000  kDA)
• Extra Low Molecular Weight (ELMW) HA = 80,000 – 110,000 Daltons (80 – 100 kDa)
• Super Low Molecular Weight (SLMW) HA = less than 50,000 Daltons (50 kDa)
• Ultra Low Molecular Weight (ULMW) HA = lesss than 6,000 Daltons (6 kDa)

The hyaluronic you want to use should be between 80,000 to 1,000,000 daltons (80 – 1,000 kDa). This seems to be the sweet spot according to studies. Anything higher won’t do much good. Anything lower might cause inflammation.

Why do I say this? Let’s break down the studies and you’ll see a pattern.

• A study on 15 subjects with rosacea found that applying 0.2% LMW HA (presumably 800 – 1000  kDA) reduced papules by 47%, decreased erythema (redness) by 51.7%, reduced burning and stinging by 65%, and decreased dryness by 78.8% after 8 weeks. (20)
• An in vitro study found that LMW HA (110 kDA – 300 kDA) improves wound injury, whereas HMW HA (1,000 – 1,400 kDa) and SLMW HA (5 – 20 kDa) had no healing effects. (21)
• An in vitro study on human skin implants found that TEWL was reduced by 15.6% with HMW HA, but increased by 55.5% with LMW HA! (22) In other words, LMW HA dried the skin out. I wish I knew what molecular weight they used, but I don’t have access to that info. My guess is it’s in the < 50,000 dalton range.
• 15 patients with facial Seborrheic Dermatitis were asked to apply LMW HA 0.2% gel twice daily. Reductions in scales, erythema, and pruritus were 66.67%, 50%, and 60%, respectively after a month. At week 8 all subjects had made improvements. Here’s a before and after of one of the participants.

SOURCE.

• This is one of the more thorough studies done on HA. It involved 66 female subjects between 30 and 60 years of age with clinical signs of wrinkles. They were asked to apply various molecular weights of 0.1% HA cream including 50, 130, 300, 800 and 2000 kDa. After one month they found that treatment with 130 kDa HA was the most effective, increasing skin elasticity by 20%. Both the 50 and 130 kDa group had significant improvement in wrinkle depth and skin roughness after 60 days. All the other molecular weights still improved elasticity and skin hydration, just less so than the two weights above (50, 130 kDa). For example, HMW HA (2,000 kDA) only increased hydration by 2.9%. (23)
• A study on 10 subjects found that applying a basic 50 – 110 kDa 2% HA lotion was helpful for “those withdrawing from topical steroidal addiction, as a result of treatment of skin conditions like eczema with topical corticorsteroids, as well as soothing Rosacea and improving appearance of fine lines and wrinkles through hydration of the skin.” (24)

So on and so forth. The takeaway being that HA between 50 – 1,000 kDa is beneficial for the skin, with ~130 kDa being the best according to human studies.

UPDATE 5/29/15: found another in vivo study that showed hyaluronic is beneficial for wrinkles and moisturization between 50 kDA and 1,500 kDa, with 50 kDA having more pronounced effects on wrinkles.

There’s also the interesting fact that very low molecular weight HA ( ≤ 25 kDA) has the ability to penetrate the skin and cause inflammation, whereas 100 kDa to 1000 kDa hyaluronic acid stays localized to the stratum corneum (i.e. outer most layer of skin). Here’s a quote from a study demonstrating that:

“In the viable epidermis, the penetration enhancement effect of 5% 5 kDa HA was even higher [than the control] with a 7.5-fold increase in BSA-RhB fluorescence intensity. Samples with 5% 100 kDa or 1 MDa HA did not show any penetration enhancement effects for BSA (bovine serum albumin).” (25)

This might be a reason super low molecular weight HA is potentially problematic (although this hasn’t been proven with convincing evidence). In other words, it causes everything else to penetrate more deeply into the skin, so if you have a compromised epidermal barrier this might be bad news. Here’s some more interesting data from that same study.

SOURCE.

This graph is a breakdown of the various percentages and molecular weights of HA on skin hydration after 6 hours. As we can see, 10% 5 kDa HA is pretty crazy! It maintains water content a lot more than the other varieties.

Interestingly enough, the graph also shows that 2% 1000 kDA HA is better than 2% 100 kDa HA in retaining water, which goes against one of the studies done on humans (in vivo). I interpret this as meaning that higher a concentration of hyaluronic acid isn’t always better. According to this study alone, it appears that hydration tends to teeter off after 2% in volume.

For this reason, if you’re formulating your own products, I recommend keeping the HA concentration below 2%.

Diameter of Hyaluronic Acid.

To further complicate things, the diameter of hyaluronic acid is also important. I won’t go into this very much. I feel like this article is getting too complex as is. But here’s a quote from research paper that summarizes it pretty well:

“Similar to most cosmeceutical ingredients, the greatest challenge with topical HA is the ability to penetrate the dermis to achieve maximal deposition. Specifically, the diameter and molecular weight of topical HA formulations have been under much investigation. Most over-the-counter HA molecules are 3,000nm in diameter, whereas the intercellular space [needed to penetrate the skin] is only 15 to 50nm. A recent study investigated the efficacy of a nanoproduct (5nm in diameter) and found a statistically significant change in the depth of wrinkles and an increase in moisture and elasticity of the periorbital region. Substances smaller than 500kDa, with sufficient oil solubility and high partition coefficient, can be absorbed into the skin. However, in contrast, larger molecules (molecular weight >500 kDa) cannot pass the cutaneous barrier.” (26)

Product Recommendations.

If I have lost you, or you are confused about what the hell all this molecular weight and diameter nonsense means — don’t worry! :p Cosmetic chemists are very intelligent and innovative people.

There are skincare products out there that take all the guess work out for you by combining various HA molecules for maximum efficacy. It’s like a jam-packed party of hyaluronic acidy goodness. One such example is the Hada Labo Hyaluronic Acid Lotion.

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Full review here. It comes with 3 different types of HA including Hydrolyzed Hyaluronic Acid, Sodium Acetylated Hyaluronate, and Sodium Hyaluronate. I have gone through two bottles of this stuff. It works great, and is something I personally use after dermarolling to speed up the healing process.

UPDATE 5/29/17: a few of you have brought to my attention the Hada Labo Premium Lotion! This is definitely something I will be trying in the future. It has FIVE different types of hyaluronic acid and comes with the addition of one of my all time favorite ingredients — 3% urea! This is a gentle keratolytic (i.e. exfoliating) agent that doubles down as an effective moisturizer.

Alright, that does it on hyaluronic acid! Hope you’ve learned something new and found this information beneficial.

Warmly,

—f.c.