Hyaluronic acid: does molecular weight really change anything?

Hyaluronic acid: you’ve almost certainly come across it. In serums, in creams, even the most generic ones at the drugstore. It’s become so common that you could almost stop seeing it.

So why is it still around? Because it does one specific job well. It’s a long chain of sugars that loves water and helps skin hold on to its hydration. It also occurs naturally in the skin, where it’s part of the matrix between cells.

That said, “hyaluronic acid” on a label doesn’t tell you much. Two products can both contain it and behave very differently, because the molecule comes in several sizes. High weight, low weight, hydrolyzed, “multi-weight”: what are all those numbers in daltons? Does it really change anything?

The question is all the more relevant for our new serum, which contains two molecular weights of sodium hyaluronate (1,600 to 2,000 kDa and 100 to 600 kDa) and a Tremella extract. We’ll explain what that means, what we know, and what we still don’t know.

First off, what is hyaluronic acid?

Hyaluronic acid (or hyaluronan, or HA to its friends) is a long chain of sugars. A polysaccharide, like the ones in Tremella that we told you about in our previous article. It’s made of two sugars that repeat: glucuronic acid and N-acetylglucosamine.

It’s found naturally in all vertebrate tissues, but skin is where we find and make the most of it. One review describes it as a key element of the matrix between cells, with a role in skin hydration. On cosmetic labels, you’ll see it written hyaluronic acid or sodium hyaluronate (the salt form).

Where does the cosmetic kind come from? It used to be extracted from rooster combs, among other sources, which are very rich in HA (yes, the dangly things on top of a chicken’s head...😖). Today, most of it is made by fermentation with bacteria. As for ours, rest assured: not a trace of rooster comb.

Like Tremella, it’s a big molecule that loves water. But here, it all depends on its size. And that’s where it gets interesting.

What is molecular weight, and why does it matter for your skin?

Molecular weight is the mass of a molecule, measured in daltons (Da). A kilodalton (kDa) is 1,000 daltons. A megadalton (MDa) is a million. Think of a string of pearls: the more pearls, the longer and heavier the necklace.

Why does it matter for your skin? Because its top layer (the stratum corneum) is a barrier, designed to keep water in and everything else out. The bigger a molecule is, the harder it is for it to get through. In dermatology, there’s a rule of thumb called the 500 dalton rule: above about 500 daltons, a molecule has a hard time crossing the top layer. Glycerin (about 92 daltons) falls below that limit. Hyaluronic acid, on the other hand, weighs from 100,000 daltons to over a million: hundreds, even thousands of times above it.

That means size decides where hyaluronic acid does its work. A high weight stays mostly on the surface, where it forms a film that holds in water. A smaller weight might go a bit further. The rule does have exceptions, though: in a 2016 study, hyaluronic acids of 20 to 300 kDa did cross the stratum corneum. That’s what makes the topic debated, and it’s what we look at next.

In the body, too, length changes all the time. Cells make long chains, which enzymes (or oxidative stress) can cut into shorter pieces, and those pieces don’t all do the same job.

The big, the small, the very small

When we talk about “high weight” or “low weight” in cosmetics, we sort hyaluronic acid into broad families. Here’s what studies describe, with numbers that vary from one study to another.

There’s no official boundary between these families. Depending on the study, “high weight” can mean more than 500 kDa, more than 1,000 or more than 1,500. “Low weight” can range from 10 to 1,000 kDa. When you read “low molecular weight” on a label, the right question is: low according to which number?

Here’s a bit more on the two main studies.

The 2011 clinical study. Seventy-six women aged 30 to 60, with wrinkles around the eyes, applied creams with 0.1% hyaluronic acid of 50, 130, 300, 800 or 2,000 kDa twice a day for 60 days, compared with a placebo. All the hyaluronic acid creams improved skin hydration and elasticity compared with the placebo. Wrinkle depth decreased significantly with the 130 and 50 kDa weights. The authors think the smallest weights may penetrate better.

The 2016 penetration study. Researchers used Raman spectroscopy to track how three hyaluronic acids of different sizes moved into human skin (taken during surgery, so outside the body). Weights of 20 to 300 kDa crossed the stratum corneum. Those of 1,000 to 1,400 kDa did not.

In the 2011 study, all weights improved hydration. So a high weight hydrates too, even if it stays mostly on the surface.

Why two molecular weights in our serum?

In our new serum, we used two molecular weights of hyaluronic acid: sodium hyaluronate at 1,600 to 2,000 kDa (a high weight) and sodium hyaluronate at 100 to 600 kDa (a smaller weight).

Where does that fall, compared with the studies? The first is a high weight: its range is close to the one that stayed on the surface in 2016 (1,000 to 1,400 kDa) and includes the 2,000 kDa tested in the 2011 clinical study. The second is smaller: the lower end of its range (100 to 300 kDa) overlaps with the weights that crossed the stratum corneum in 2016, and compares with the 130 and 300 kDa of the 2011 study. The upper end of its range, up to 600 kDa, wasn’t tested in either study.

Some studies define “low weight” as anything up to 100 kDa, and the lower end of our range touches that limit.

Why two? The high weight stays mostly on the surface, where it forms a film that holds in water. The smaller weight, meanwhile, penetrates the stratum corneum to hydrate more deeply. So you hydrate the surface, and the inside.

It also lets us make one ingredient work in two ways. And with Tremella in our new serum, that makes a trio of ingredients that love water, each with its own size and structure: two weights of sodium hyaluronate, plus the polysaccharides of Tremella.

And what about Tremella?

If you read our article on Tremella, you’ll remember we mentioned a 2026 study comparing a Tremella extract with hyaluronic acid on human fibroblasts in the lab. That study used a high-weight hyaluronic acid (1.5 to 2.2 million daltons). The manufacturer of the Tremella extract tested, for its part, reports an average weight of about 1,000 kDa. Two big molecules, then.

For Tremella, molecular weight is an open question too: a 2021 review reports weights from 8,000 daltons to 6 million daltons, depending on the source and the extraction method. And it lists the effect of molecular weight on absorption through the skin among the questions still to be explored.

And that’s where our serum comes in. Two sizes of sodium hyaluronate, each with its own behavior on the skin, and a Tremella extract, this jellyfish mushroom that has long had its place in Asian kitchens and traditions. A trio of actives that love water, no fuss, to slip into your routine before your oil serum. Try it, then tell us what your skin thinks.

FAQ

“A dalton? Like Lucky Luke’s Dalton brothers?”

Nope, haha. The unit is named after the chemist John Dalton, who worked on the mass of atoms. No relation to Joe, Jack, William and Averell.

“Are hyaluronic acid and sodium hyaluronate the same thing?”

Almost. Sodium hyaluronate is the salt form of hyaluronic acid, and you’ll see both names on labels. Neither one tells you the size of the molecule: in both cases, molecular weights vary a lot.

“Is smaller better?”

It depends on what you’re after. In the 2011 clinical study, all weights improved hydration, and the smallest were associated with shallower wrinkles. On the other hand, very small fragments are debated. See above.

“Does it fill in wrinkles like an injection?”

No. Injections use a hyaluronic acid gel (often modified to last longer), placed in the skin by a professional. A serum is applied on the skin, and penetration studies mostly look at the top layer and the epidermis.

“Does my hyaluronic acid come from animals?”

For most of today’s cosmetic products, no: it’s mostly made by fermentation with bacteria.

“What about glycerin? Doesn’t it do the same job?”

Partly. Glycerin is another humectant: it also attracts and holds water. It’s much smaller than hyaluronic acid, and very well studied. A 1986 study describes it diffusing into the top layer of the skin and forming a reservoir there. You’ll sometimes read that it beats hyaluronic acid for hydration: we couldn’t trace that back to a study we can verify, so we’re not repeating it. The two aren’t mutually exclusive.

Discover our hydrating Tremella and hyaluronic acid serum

To learn more

• Pavicic T. et al. (2011). Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. Journal of Drugs in Dermatology, 10(9).
• Essendoubi M. et al. (2016). Human skin penetration of hyaluronic acid of different molecular weights as probed by Raman spectroscopy. Skin Research and Technology, 22(1).
• Waggett S. et al. (2024). Update on Low-Molecular Weight Hyaluronic Acid in Dermatology: A Scoping Review. EMJ Dermatology, 12(1).
• Widgerow A.D. et al. (2022). Designing topical hyaluronic acid technology: Size does matter…. Journal of Cosmetic Dermatology, 21(7).
• Kavasi R. et al. (2017). HA metabolism in skin homeostasis and inflammatory disease. Food and Chemical Toxicology, 101.
• Wolosik K. et al. (2026). Tremella fuciformis Extract Evokes Similar Effect as Hyaluronic Acid on Wound Healing but Through Different Mechanisms in Human Dermal Fibroblasts. Molecules, 31(13).
• Ma X. et al. (2021). A review on the production, structure, bioactivities and applications of Tremella polysaccharides. International Journal of Immunopathology and Pharmacology, 35.
• What is hyaluronic acid and how does it work? (Lab Muffin Beauty Science), for the industrial sources of hyaluronic acid.

• Hydration of the stratum corneum. International Journal of Cosmetic Science, 1986, 8(6), for glycerin.