Polynucleotides or hyaluronic acid: what is better for skin quality?

In short: It depends on what you want to achieve. Hyaluronic acid binds water and immediately gives the skin moisture and plumpness. Polynucleotides work a level deeper: they stimulate skin cells to renew themselves. When it comes to volume and quick plumping, hyaluronic acid has the advantage. When it comes to actual skin quality – texture, pores, elasticity, density – polynucleotides show an advantage in studies. In practice, it's rarely an either-or: the two complement each other.

When delving into modern skin treatments, you'll inevitably encounter these two terms. Both are introduced into the skin, both aim to "improve" it – and yet they are fundamentally different. Here, we'll explain from scratch what the difference is, what the research says, and how you can make the right choice for yourself.

Two active ingredients, two completely different tasks

Imagine your skin like a mattress. Hyaluronic acid is the water that keeps the mattress plump and cushioned. Polynycleotides are more like a signal to the craftsmen who repair and rebuild the mattress's structure.

Both are not foreign bodies, by the way. Hyaluronic acid occurs naturally in your skin and is one of the most important moisture reservoirs. Polynucelotides are purified DNA fragments that serve the body as building blocks and signal transmitters. They come from a natural source – more on that shortly.

What hyaluronic acid does (and doesn't do)

Hyaluronic acid is a marvel of hydration. A single gram can bind large amounts of water. This is precisely what makes it so valuable: where hyaluron is, the skin appears plumper, smoother, and fresher.

This effect is primarily physical. Hyaluron attracts and retains water. With cross-linked variants, volume is added – these are the classic fillers. With non-cross-linked variants, the so-called skin boosters, moisture and a finer skin texture are the priority. We explain the difference between these two HA types in detail in the article. Hyaluronic acid: cross-linked vs. non-cross-linked.

What Hyaluron alone cannot achieve: It does not fundamentally rebuild new skin. It hydrates and plumps – but it does not send a strong signal to cells to renew themselves. This is exactly where polynucleotides come in.

What makes polynucleotides different

Polynucleotides work at the root. Instead of just binding water, they activate fibroblasts — the cells that produce collagen, elastin, and your body's own hyaluronic acid. With age, these cells become fewer and slower. Polynucleotides form a water-rich scaffold in the tissue, creating an ideal environment that stimulates these cells.

In addition, there are two properties that one would not expect from a pure moisturising active ingredient: polynucleotides have antioxidant and soothing effects on irritated skin. The result builds up slowly – over weeks, not hours. However, this is about genuine regeneration, not just plumping.

You can read how this works in detail and where the active ingredient comes from in the foundational article What are polynucleotides?.

The direct comparison: What do the studies say?

This is where it gets interesting, as there's an important study that tested both directly against each other. In a randomised, double-blind, split-face study (each half of the face received a different preparation), researchers compared polynucleotides with a hyaluronic acid preparation for the eye area. The result: both improved elasticity and hydration. For skin roughness and pore volume, the polynucleotide side showed a greater improvement – with no serious side effects.

A recent review from 2026 soberly summarises the current research: For structural correction – meaning volume – hyaluronic acid remains superior. For skin quality parameters such as elasticity, hydration, and fine lines, polynucleotides show consistent improvements with a good safety profile. At the same time, direct comparison studies are still rare and often small – the research is young.

Also: better for skin quality?

If your question is "What fills a wrinkle or provides volume?" – then it's hyaluronic acid. If your question is "What improves the quality and resilience of my skin from the ground up?" – then the data points to polynucleotides.

Exactly why polynucleotides are so well-suited to a pre-aging approach: it's not about masking anything, but about strengthening the skin's own function before visible signs emerge. And because polynucleotides stimulate the skin to produce more hyaluronic acid itself, the two active ingredients are essentially working together. Why "either/or" is often the wrong question, we'll delve into separately.

How we decide in the clinic

At the alestetics® clinic in Zurich, we work with polynucleotides (PolyPhil™) and the NCTF® nutrient complex for deep hydration. What makes sense for you depends on your skin, your age, and your goal — not a trend.

We always start with an analysis, not a treatment. During the free AURA 3D skin analysis, we examine your skin in depth to see whether it needs hydration, cell renewal, or both.

Read on

• What are polynucleotides? Effect, Origin & Process
• Hyaluronic acid: cross-linked vs. non-cross-linked explained simply
• Does hyaluronic acid cream really work?
• Plinest, PolyPhil, Rejuran, Nucleofill: the brands compared
• Polynucleotides under the eyes: against dark circles