How is long chain hyaluronic acid absorbed?

One of the most common and reasonable questions about using oral long-chain hyaluronic acid as a joint supplement is very simple:

How can something so large possibly be absorbed in the first place?

And it's a fair question, long chain hyaluronic acid is a very large molecule, millions of Daltons, compared with water 18Da or glucose 180Da and far bigger than vitamins, minerals and other small nutrients we know are absorbed.

Let’s clear one thing up first: long-chain hyaluronic acid IS absorbed

One of the most elegant demonstrations comes from a study* in which scientists attached weakly radioactive labels to hyaluronic acid molecules before administering them orally to animals.

Using radiation-sensitive imaging, researchers were able to track the movement of the labelled hyaluronic acid molecules through the body over time. What they observed was striking: radioactivity appeared not just in the gut, but quite quickly after, in connective tissues such as joints, skin, eyes, muscle, and bone.

To rule out alternative explanations, the experiment was repeated using the radioactive labels without any hyaluronic acid and this time the labels were simply excreted, with no meaningful absorption.

The conclusion: the radio-label was travelling with the hyaluronic acid and tracking its absorption and distribution in the body.

Absorption, therefore, is proven. What is even more interesting is how hyaluronic acid is absorbed—and the clues left by the route taken by the radio label as it enters the body.

The Liver Should Have Lit Up (But Didn’t)

Under normal circumstances, nutrients absorbed from the intestine enter the portal bloodstream which carries them directly to the liver. The liver acts as a metabolic filtration unit and storage, rapidly processing, modifying, or breaking down nutrients as they are absorbed from the gut.

If hyaluronic acid were absorbed via this conventional route, we would expect to see high concentrations of radio-label accumulating in the liver early on.

But that didn’t happen.

Instead, imaging showed minimal dignal from the liver. Even more surprisingly, labelled hyaluronic acid appeared in connective tissues before it was detectable in the bloodstream at all.

This immediately rules out standard portal absorption as the primary route.

So how did hyaluronic acid reach connective tissues without first passing through the blood?

The Lymphatic System isn't classically associated with digestion 

To answer this, we need to consider how the body handles large or structurally complex molecules.

Some substances—particularly fats—are poorly suited to direct absorption into the bloodstream becasue they don't mix well with the water that dominates in body tissues. Instead, fats in the gut are taken up by intestinal cells and routed directly into the lymphatic system, a parallel transport network that runs alongside the blood circulation.

From there, lymph fluid gradually drains into the bloodstream, bypassing the liver entirely.

This lymphatic route is:

• slower

• more selective

• oriented toward tissue distribution rather than rapid circulation

Crucially, this pathway explains all the clues observed in the hyaluronic acid studies:

• minimal liver accumulation

• delayed appearance in the blood

• early presence in connective tissues

For large molecules, lymphatic transport is not a workaround—it is often the preferred route.

But Hyaluronic Acid Isn’t Fat — So Why This Route?

This is where hyaluronic acid’s physical properties become important.

In a watery environment, long-chain hyaluronic acid behaves like a microscopic gel. Its structure allows it to bind water, form networks, and interact with surfaces in a way small molecules cannot.

Additionally, Hyaluronic acid is bioadhesive. This means it has a natural tendency to interact or stick to cell surfaces, including the epithelial cells lining the gut. These interactions may facilitate its uptake into intestinal cells and therefore its subsequent routing into the lymphatic system rather than directly into the bloodstream.

In other words, hyaluronic acid doesn’t need to resemble fat chemically to behave like a “large structural molecule” biologically.

The lymphatic system exists precisely to deal with molecules of this nature.

Why this matters and what to expect

Lymphatic transport has an important consequence:

it favours gradual, distributed delivery rather than sharp concentration spikes.

This helps explain why changes associated with long-chain hyaluronic acid are often subtle, progressive, and cumulative rather than immediate. The molecule is not flooding the bloodstream or forcing a rapid response. It is being distributed slowly to tissues that naturally utilise it.

From a biological perspective, this is entirely consistent with the normal role of hyaluronic acid in the body—as a structural, regulatory component of connective tissues rather than a fast-acting agent.

Where This Leaves Us

To summarise:

• Long-chain hyaluronic acid is absorbed after oral administration

• It does not follow the typical portal blood–liver route

• Evidence strongly supports lymphatic uptake

• This explains both its tissue distribution and its gradual effects

 

*Balogh L, Polyak A, Mathe D, Kiraly R, Thuroczy J, Terez M, Janoki G, Ting Y, Bucci LR, Schauss AG. Absorption, uptake and tissue affinity of high-molecular-weight hyaluronan after oral administration in rats and dogs. J Agric Food Chem. 2008 Nov 26;56(22):10582-93. doi: 10.1021/jf8017029. PMID: 18959406.