Polynucleotides vs hyaluronic acid — the difference explained without the hype

These two ingredients get bundled together because they’re both used in “hydration” and “anti-ageing” conversations. But they’re solving different problems — and in real formulas, they’re often used together for a reason.

Hyaluronic acid is primarily about water management — improving hydration gradients so skin looks and feels more comfortable.

Polynucleotides are more about skin quality and recovery — supporting the environment your skin uses to stay resilient over time (barrier stability, extracellular matrix support, and the conditions that help skin recover from daily stress).

If you’re deciding what to add next, or you keep layering products and still feel like nothing is “sticking”, this comparison will help you choose based on mechanism rather than trend.

This page supports our pillar guide: Polynucleotide Skincare Explained: What It Is, How It Works & How to Use It. If you want the full routine build (including device-compatible options), that’s the best place to start.

What Are Polynucleotides?

Polynucleotides are chains of nucleotides — the small units that make up DNA and RNA. In skincare, the term usually refers to purified nucleic-acid fragments (often listed as Sodium DNA) used in routines focused on skin quality: resilience, comfort, and the way skin behaves over weeks rather than hours.

They’re sometimes discussed alongside clinic treatments (you’ll hear “PN” in professional settings), but topical polynucleotide skincare is best thought of as a routine ingredient — something you use consistently to support barrier function and recovery, rather than chase a dramatic overnight effect.

From a practical mechanism point of view, polynucleotides are typically used to support the skin’s regenerative environment:

• Barrier support: helping reduce the cycle of dehydration → irritation → more dehydration.
• Extracellular matrix support: the “scaffold” around cells that influences how well skin holds structure and hydration.
• Fibroblast-friendly conditions: fibroblasts are cells associated with maintaining collagen, elastin, and matrix components.

In practice, many well-formulated polynucleotide serums also include advanced hydration support (including multiple forms of hyaluronic acid) so surface hydration and long-term comfort are addressed together. If you’re using a serum like Pure Tone Polynucleotide Serum, you may not need to add a separate HA serum unless you know your skin benefits from an extra hydration step.

If you want the deeper explanation (and how to build a routine you’ll actually keep up), use the pillar: Polynucleotide Skincare Explained.

What Is Hyaluronic Acid?

Hyaluronic acid (HA) is a sugar-based molecule found naturally in skin and connective tissues. Its headline skill is simple: it binds water.

In topical skincare, HA helps support hydration by:

• Holding water in the upper layers: improving the hydration gradient that makes skin look smoother.
• Reducing “tight” feel: especially after cleansing, travel, dry indoor environments, wind, or active ingredients.
• Softening dehydration lines: lines that look deeper when the surface is dry (not the same thing as structural wrinkles).

A useful way to think about HA is that it’s a hydration manager. It doesn’t “teach” skin to behave differently long-term on its own — but it can make skin visibly calmer and plumper quickly, which is why it’s everywhere.

Practical note: HA works best when you seal it in with a moisturiser. Without that, it can feel like it “disappears” by midday. If your main serum already contains multiple forms of hyaluronic acid, you’ll usually get the benefit without needing a separate HA product — unless your skin is exceptionally dehydration-prone.

How They Work in the Skin (Side-by-Side Comparison)

The main confusion is that both ingredients can make skin feel better — but for different reasons.

HA improves water distribution and surface comfort. Polynucleotides support recovery and skin quality over time. If you’ve ever felt like your skin “drinks” HA and still feels fragile, that’s a clue you may need more barrier/regeneration support rather than simply stacking hydration layers.

Hydration vs Regeneration – The Core Difference

If you want a clean mental model, use this:

That’s why you’ll often see HA in routines that need quick comfort, and polynucleotides in routines built around long-term resilience — including when people are using devices, exfoliants, or professional treatments and want skin to stay calm and functional.

Which Is Better for Ageing Skin?

“Ageing skin” isn’t one thing. Common drivers we see day-to-day are:

• Dehydration cycles: dry indoor environments, wind, travel, over-cleansing, and active ingredients.
• Barrier instability: skin that looks fine one day and irritated the next.
• Slower recovery: redness lingers, dryness returns quickly, texture looks less even.
• Structural changes: loss of elasticity and firmness over time.

If your “ageing” concerns are mostly dehydration lines and tightness, hyaluronic acid often gives the most immediate improvement.

If your concerns are more about skin quality — resilience, comfort, and that “held together” look — polynucleotides tend to be the more targeted choice.

The most realistic approach for many people is not choosing one forever, but choosing a core and then adding support:

• Core = polynucleotide-led routine (for stability and long-term quality) — for example, a consistent polynucleotide serum as your daily treatment step.
• Support = extra HA (optional) for seasonal dryness, travel, retinoid nights, or whenever skin is simply thirstier — especially if your main serum does not already contain hyaluronic acid.

Can You Use Both Together?

Yes — and for many people, that’s where routines start to make sense. The only nuance is whether your main serum already contains hyaluronic acid.

If your routine starts feeling sticky or heavy, the fix usually isn’t adding more steps — it’s using less product per step and keeping layers thin.

Who Should Choose What?

Here’s the most practical way to decide — based on the problem you’re actually trying to solve (and whether your main serum already includes hyaluronic acid).

Final Thoughts

FAQs

Are polynucleotides better than hyaluronic acid?

Not objectively — they do different jobs. Hyaluronic acid is mainly hydration support. Polynucleotides are used more for skin-quality support over time (barrier comfort, resilience, recovery).

If your concern is dehydration, HA can feel “better” quickly. If your concern is ongoing skin fragility or uneven texture, polynucleotides may be the more targeted choice.

Do polynucleotides hydrate skin?

They can support hydration indirectly by improving barrier comfort and reducing water loss behaviours over time. But their main role isn’t “instant plumping” the way HA is.

Also worth noting: many polynucleotide serums include multiple hyaluronic acid types within the same formula, so you may still get strong hydration support without adding a separate HA serum.

Can you layer polynucleotides and hyaluronic acid?

Yes. A simple order is: cleanse → polynucleotide serum → optional HA serum → moisturiser.

If your main polynucleotide serum already contains hyaluronic acid, treat the extra HA step as optional — use it when your skin is thirstier rather than assuming you always need it.

Which works faster?

Hyaluronic acid usually feels faster because hydration changes can be visible within hours.

Polynucleotides are more gradual — think weeks of consistent use, with the goal being improved comfort, stability and skin quality rather than an overnight shift.

Are polynucleotides only for mature skin?

No. They’re often chosen for mature skin because “skin quality” matters more over time, but they can also suit younger skin that’s stressed, reactive, post-treatment, or struggling with barrier instability.

Can polynucleotides replace injectable treatments?

Topical skincare can support skin quality, hydration stability and barrier function, but it doesn’t replicate the structural changes of injectables.

A realistic way to frame it is: skincare supports the day-to-day condition of the skin, and can help maintain results and comfort alongside professional treatments — not replace them.

Is hyaluronic acid enough on its own?

For simple dehydration, it can be. But if skin feels reactive, thin, or slower to recover, hydration alone may not address the underlying barrier or structural environment.

Many people find HA works best as support — either within a more complete formula, or layered when skin needs it.

Can you use polynucleotides with retinol?

Yes. Polynucleotides are often used in routines that include retinoids because they focus on barrier comfort and recovery support.

If using retinol, keep layers thin and prioritise moisturiser. If your serum already includes multiple hydrating components, you may not need an extra HA serum on the same night unless you feel dry.

Do polynucleotides stimulate collagen?

Topical polynucleotides do not “force” collagen production in the way in-clinic procedures might. Their role is more about supporting a fibroblast-friendly environment and extracellular matrix stability over time.

The effect is gradual and related to skin quality rather than dramatic structural change.

Why does hyaluronic acid sometimes feel like it dries my skin?

If HA is applied without a moisturiser on top, water can evaporate more easily — especially in dry indoor air.

Always seal hydration layers with a moisturiser to reduce transepidermal water loss.

Are polynucleotides suitable for sensitive skin?

Many routines for reactive or compromised skin include polynucleotides because the focus is barrier comfort and recovery support rather than exfoliation or stimulation.

As with any product, patch testing is sensible if skin is highly reactive.

Can hyaluronic acid replace moisturiser?

No. Hyaluronic acid binds water, but moisturisers reduce water loss and support the barrier.

They perform different roles and are often best used together.