It sounds too good to be true: that simply taking a supplement can reverse skin wrinkles. So is this really possible? Well, after some initial controversy with Hyaluronic Acid supplements, it looks like the answer is a resounding yes—but only if it’s used correctly.
Table of Contents
- What is it?
- Why think it could help with aging skin?
- The wall – but is it bioavailable?
- Studies on aging skin
- What about safety?
- Use
- Reference List
What is it?
Hyaluronic Acid (HA) has gained a lot of attention for its potential to help skin look smoother, plumper, and more youthful. In this article, we’re going to look at the research on whether hyaluronic acid supplements really work to reduce wrinkles and why there was so much controversy in the first place.
Hyaluronic acid is a natural compound found especially in our skin, joints, and eyes. One of its stand-out features is its ability to retain moisture. It’s like a sponge with incredible capacity. Just a quarter teaspoon of hyaluronic acid can absorb one and a half gallons of water.
It provides crucial structural support in the skin, keeping it plump, hydrated, and smooth
In other words, it helps keep our skin looking youthful. Unfortunately, levels of hyaluronic acid in the skin slowly decrease with age. Someone at 75 years of age has only a quarter of the hyaluronic acid in their skin as someone who is 19 [1].
Imagine your skin as a mattress. When you're young, it’s full of support and bounce, thanks to high levels of hyaluronic acid. As you age, it’s like the mattress losing some of its springs, becoming less supportive and more prone to wrinkles.
The wall – but is it bioavailable?
That leads to a natural question. Is it possible to somehow restore levels of hyaluronic acid, rejuvenating the skin?
One way to test this out would be to inject hyaluronic acid directly into the skin. This has become an increasingly popular cosmetic procedure. It’s commonly used to address signs of aging in the face. And the evidence suggests it works. One recent meta-analysis examined 13 studies on the procedure. The authors found injecting hyaluronic acid causes a significant improvement in facial skin quality [2].
And that’s good news. Because it validates the idea that adding hyaluronic acid back into the skin can restore its condition. But injecting hyaluronic acid is expensive. It also only targets a small area of the skin. So what about another route to boosting our levels of this key compound? Would taking supplements orally work?
Initially, there was a big reason to think the answer would be “no.” To see why, we need to talk about molecular weight. A molecule is a collection of atoms bonded together in a certain way. The weight is about how big this collection is. Structurally, hyaluronic acid is like a chain built from simple links. And just like a chain, molecules of hyaluronic acid can be of different lengths. Long ones are heavy; they have a high molecular weight. Short ones have a low molecular weight.
Scientists thought high molecular weight forms of hyaluronic acid would be best for oral supplements. The idea was that they’d be more stable and less likely to be immediately broken down through digestion. The hope was that more would be able to make it intact to sites like the skin where it would be useful.
But there’s a catch-22 here. Those high molecular weight forms of hyaluronic acid had big molecules—maybe too big to pass through the intestinal wall. And if that proved to be the case, the fear was that the supplement would just pass through the digestive system without providing any benefits.
We just didn’t know for sure what would happen until we did some research.
Early experiments were encouraging. A groundbreaking study was published in 2009. It involved oral hyaluronic acid supplementation in rats and dogs. Researchers used a high molecular weight form. They tagged hyaluronic acid with a radioactive substance so they could see where it went. They found evidence it made its way directly to connective tissue throughout the bodies of the animals [3].
It seemed to stay intact and make it through the gut barrier. The authors pointed out these results suggest hyaluronic acid may indeed be helpful in supplements designed for joint and skin health in humans [4].
Another study, citing human experiments, agreed with this conclusion. Hyaluronic acid in an oral supplement looks like it is absorbed whole and distributed to the skin [5].
This kind of evidence led me to opt for the more expensive, high-molecular weight hyaluronic acid when I first started taking it as a supplement.
But a study that came out in 2023 showed us this wasn’t what was going on after all. Our assumptions about how hyaluronic acid worked as a supplement were all wrong.
Here’s what they found. First, high molecular weight hyaluronic acid isn’t absorbed at all [6].
That doesn’t mean nothing gets absorbed. But the story is more complex. The high molecular weight hyaluronic acid first has to be broken down. This happens in the stomach, as those long chains get chopped into shorter lengths.
But here’s where it gets interesting. These shorter lengths, called middle-weight hyaluronic acid, aren’t absorbed, either. For this study, researchers used two kinds of mice. One group had normal gut bacteria and another group had no gut bacteria. In the no-bacteria group, no hyaluronic acid was absorbed. It was broken down in the stomach and then just passed through.
In the group with normal bacteria, however, things went differently. Here the medium-weight hyaluronic acid got broken down even further by gut bacteria. And this finally gets us to a form that can be absorbed [7].
So it turns out absorbing hyaluronic acid is like pulling apart a LEGO structure. The digestive system breaks down the long chains of high-molecular-weight hyaluronic acid into smaller pieces. It’s just like you might break down a LEGO castle into individual bricks before building something else. These smaller pieces can then be absorbed and used by the body.
However, even after this process, the bioavailability of hyaluronic acid is still very low—around just 0.2% [8].
Why are these results so different from earlier studies that found long chains of hyaluronic acid can be directly absorbed?
The authors of the 2023 study think they know. They explain that the prior absorption studies used methods that weren’t accurate enough. They couldn’t tell if those radioactive tags they used ended up attached to a molecule of hyaluronic acid or just one of its metabolites. They might have even been attached to nothing [9].
It’s like putting a tracking tag on the foot of a bird. When it’s released into the wild, we can see the tag show up on a monitor. But we don’t know if we’re seeing the location of the bird, its severed foot, or a tracking tag that has fallen off.
In contrast, the 2023 study used the latest tagging technology and provides a more accurate representation of how hyaluronic acid is processed in the gut.
So where do these results leave us? The first thing that’s clear is there’s no reason to buy expensive high-molecular-weight hyaluronic acid. It doesn’t get absorbed in that form but has to be broken down anyway.
But more importantly, the study showed only a very small amount of the broken-down pieces are bioavailable. So the early assumption—that orally ingested hyaluronic acid is directly making its way to our skin—is wrong.
Studies on aging skin
So if hyaluronic acid isn’t making it to our skin, do oral supplements do any good? Or are they just a waste of money?
Researchers have been testing out oral hyaluronic supplements for their impact on skin since the early 2000s. This was long before we had the full picture in terms of absorption.
When examining the research, we care about the human, randomized, placebo-controlled trials. This is where one group of people take the hyaluronic acid, and another group take a placebo or dummy pill. Then we can compare whether there are any benefits to the skin.
Several smaller studies were carried out in Japan. They focused on dry skin. They consistently showed that hyaluronic acid supplements improved skin moisture [10].
This is encouraging. As we saw earlier, hyaluronic acid is especially connected to retaining moisture.
But what about wrinkles? In 2001, a small trial suggested that hyaluronic acid decreased wrinkle depth compared to a placebo. Similar results were found in a small 2007 study and again in 2017 in a study involving 60 people [1].
You’re probably wondering how wrinkle depth is measured. In the 2017 study, they applied a chemical to make a mold of the skin near the corner of the eye. Once dried, the molds were peeled off and scanned. That provided an objective measurement of wrinkles. The analysis showed a clear difference between the group taking hyaluronic acid and the placebo group.
All good news so far. There’s a controversy about safety when it comes to hyaluronic acid, but we’ll get to that in a moment.
Interestingly, the 2017 study also compared the effects of different molecular weights of hyaluronic acid. Now that you know about the 2023 study, I bet you can predict what happened. There was no difference between the higher vs. lower molecular weight versions. Both groups had similar improvements in skin wrinkle depth compared to the placebo group [1].
That’s again because hyaluronic acid gets broken down by the gut bacteria into metabolites before it’s absorbed.
Let’s look quickly at three more studies. A 2021 randomized controlled trial of 40 people also showed benefits [11].
Here I want to pause over something important about the last two studies we’ve looked at. They were both funded by the Kewpie Corporation [11]. That raises the possibility of bias. The Kewpie Corporation sells hyaluronic acid for other companies to use in applications like supplements. It helps that these experiments used objective measures of skin wrinkles. And it also helps that we see similar results from other researchers who aren’t connected to this company.
For example, a 2021 study published in the European Journal of Dermatology found wrinkles decreased by 18.8% with hyaluronic acid supplements. This compared to a non-significant reduction of 2.6% in the placebo group [12].
Finally, a larger 2023 study of 129 people again demonstrated skin improvements from hyaluronic acid supplements [13].
So this is really interesting. Even though analysis shows hyaluronic acid is broken down and has poor bioavailability, there are plenty of studies showing it helps with skin aging. This just shows us that the mechanism isn’t what we originally supposed. As the 2023 study says, it seems to have something to do with indirect rather than direct effects [9].
So we’re still not 100% sure about the exact mechanism, but it seems that it’s the broken-down hyaluronic acid metabolites that are providing the benefits to our skin. And regardless, we have good evidence from human randomized controlled trials that it works.
What about safety?
But that raises a potential worry. If we aren’t sure exactly how it’s working, do we know that it’s safe?
The big safety concern that you’ll hear about on social media is cancer. In single cell studies, when hyaluronic acid is given to cancer cells, it appears to accelerate cancer growth [14].
Which doesn’t sound great. However, when hyaluronic acid supplements are given to mice who already have cancer, there’s no difference. Researchers concluded hyaluronic acid is safe [15].
A panel of experts assembled in 2023 to look at the safety of oral hyaluronic acid agreed. After examining the literature, they found no reports of adverse health effects from hyaluronic acid supplements [16].
Use
So hyaluronic acid is safe. And we also have good evidence that it’s effective. If we want to try it, which form is best?
As explained, hyaluronic acid is broken down into building blocks our bodies can use.
So when designing MicroVitamin, I elected to use sodium hyaluronate 200 mg due to its enhanced stability and solubility and smaller molecular size [17].
The 200 mg dose is the most commonly used dose in the existing human trials.
But just because I take a supplement does not in any way mean that you should as well.
There are other proposed benefits from hyaluronic acid. It is claimed to help with wound healing, arthritis, and eye health. But the randomized controlled trial results are conflicting. Large, longer-term trials are needed before we can be confident of the effects.
Reference List
Below are the study links, listed in the order they appeared in the article:
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522662/
2. https://pmc.ncbi.nlm.nih.gov/articles/PMC10082573/
3. https://pubs.acs.org/doi/10.1021/jf8017029
4. https://pubs.acs.org/doi/10.1021/jf8017029
5. https://pmc.ncbi.nlm.nih.gov/articles/PMC3512263/
6. https://www.sciencedirect.com/science/article/abs/pii/S0144861723003454?via%3Dihub
7. https://www.sciencedirect.com/science/article/abs/pii/S0144861723003454
8. https://www.sciencedirect.com/science/article/abs/pii/S0144861723003454
9. https://www.sciencedirect.com/science/article/abs/pii/S0144861723003454
10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110621/
11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308347/
12. https://pubmed.ncbi.nlm.nih.gov/34933842/
13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10661223/
14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8730721/
15. https://pubmed.ncbi.nlm.nih.gov/24894153/
17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299688/
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always consult with a qualified healthcare professional before making changes to your supplement routine.
