Polynucleotides vs filler. When each one makes sense.

A patient asked me last week, mid-consultation, whether polynucleotides were "just a kind of new filler." I told her no, and then realised I needed a better answer than that. The two are routinely conflated by patients who have read the same TikTok video, and routinely conflated by clinics that should know better. The conflation matters because the wrong choice between them is the single most common reason aesthetic patients leave a clinic mildly disappointed.

This is the long answer. I want to explain what each treatment actually does, where the published evidence agrees and where it is genuinely thin, and how I decide which one to recommend in our clinic in Battersea. By the end of it, if you read it carefully, you should be able to walk into any consultation in London and know whether the clinician opposite you understands the distinction or is selling you the thing they have on the shelf.

Two molecules, two completely different jobs

Hyaluronic acid filler is cross-linked HA gel. When it is injected into the dermis or subcutaneous plane, it occupies space. That space displaces the surrounding tissue and creates a visible volume change. The gel attracts water, so the effect intensifies slightly over the first two weeks. Over the next 9 to 18 months the cross-links break down through hyaluronidase activity, the gel breaks up, and the volume returns to baseline. That is the whole mechanism. It is well understood and it has been the workhorse of facial aesthetics for two decades.

Polynucleotides are something biologically different. They are short, purified DNA fragments (typically from salmon or trout testes, processed under medical-grade conditions). When injected into the mid-deep dermis they do not occupy meaningful space. What they do, according to the mechanistic literature, is signal to fibroblasts (the cells that produce collagen, elastin and extracellular matrix) to upregulate their activity. The fibroblast effectively wakes up. Over six to twelve weeks after a course of treatment, the surrounding skin tissue changes its biological quality.

If filler is a piece of architecture you install in the wall, polynucleotides are a signal you send to the bricklayers who built the wall in the first place, asking them to lay a few more bricks.

What the evidence does and does not show

Let me be careful here, because in our field there is a lot of overstatement on both sides.

For filler, the evidence base is large, multi-decade, and rich with both safety data and efficacy data. The mechanism is straightforward enough that the studies translate cleanly between products of the same class. We know how HA filler behaves in skin. We know its complication profile (the most serious being vascular occlusion) and we know how to manage those complications.

For polynucleotides, the literature is younger and shallower. A systematic review published in the Journal of Cosmetic Dermatology earlier this year (Lampridou et al., 2025) gathered the available trials and described the population: nine studies of low to moderate quality, 219 patients across the lot, generally positive outcomes in skin texture, hydration and elasticity, no serious adverse events³. A broader narrative review published in Applied Sciences in late 2025 covers the molecular mechanism and clinical applications more widely⁴. The picture is consistent: polynucleotides do something, the effect is real, and the evidence is not yet at the maturity of HA filler evidence.

The most useful comparison study is from 2020, and it is the one I cite most often in clinic. Cavallini and colleagues tested an HA-polynucleotide combination filler against a plain HA filler in vitro and in mouse skin¹. The HA-PN combination drove more fibroblast migration and more collagen synthesis than HA alone. A separate randomised, double-blind, split-face trial in 2020 compared polynucleotide injectables to HA filler in the periocular area². Both improved skin elasticity and hydration. Polynucleotides outperformed on skin roughness and pore volume measures.

What none of this proves is that one treatment "beats" the other in any general sense. They were measured on different outcomes, in different populations, with different goals. What it does prove is that the mechanisms are distinct and that for outcomes related to skin quality (texture, hydration, fine line, elasticity), polynucleotides have a credible and growing evidence base. For outcomes related to volume (shape, projection, replacing lost fat pad), the case for filler remains stronger.

A practical comparison table

The table below is the one I print and hand to patients in consultation. It does not appear in the marketing material because marketing prefers a clean winner. Clinic conversations need both columns visible.

How I decide in a consultation

The first question I ask is not which treatment do you want. It is what bothers you when you look in the mirror. Patients who answer with words about shape (sunken, flat, lost my cheekbones) are usually filler candidates. Patients who answer with words about quality (tired, dull, dehydrated, lines around the eyes, under-eye looks dark) are usually polynucleotide candidates. About thirty per cent of patients have a mix of both, and need a sequenced plan: polynucleotides first to improve the skin quality, filler later if a remaining volume issue is still bothering them once they can see clear skin in the mirror.

The order matters more than the products. Patients who get filler first on a face with poor skin quality often come back unhappy because the new volume sits inside an envelope that still reads as tired. Treating the skin quality first sometimes removes the perceived need for filler altogether. I have had patients book a course of polynucleotides intending it as the pre-filler phase, finish the third session, look at themselves in the mirror, and decide they do not need the filler appointment after all. That is a clinical win even though it is not a commercial one.

The wrong order, in the other direction, is harder to fix. You can dissolve filler, but you cannot un-do the conversation in which a patient who needed skin quality work was sold volume instead.

What polynucleotides specifically do not do

This is the section that the product marketing tends to skip. Polynucleotides are not a miracle treatment. They will not lift a brow. They will not project a jawline. They will not replace a lost fat pad. The patients who do best with them are the ones who come in with realistic expectations about what skin quality work can deliver. The patients who do worst are the ones who heard about them on TikTok and assumed they were a "needle-free face lift," which they are not.

The other thing they do not do, despite occasional product claims, is permanently change the skin. The effect builds over the course of three sessions and peaks at around three months. Then it slowly fades over the next six to nine months. Maintenance is part of the plan. We typically recommend a refresher session every six to nine months once the initial course is complete.

The price comparison, briefly

At Melatone, polynucleotides (Nucleofill) are sold as a Course of 3 from £540, which is £180 per session for the eye area and rises to £900 for the deep dermal and hair indications. Dermal filler is priced per syringe, typically £250 to £450 per 1ml depending on the product and area. A patient who needs both will often find the polynucleotide course is a smaller commitment than the volume of filler that would be needed to achieve a similar overall result. A patient who only needs one will find the cost depends entirely on which one.

I list our full polynucleotide pricing on the main Nucleofill page. Filler pricing is listed by area on Treatwell.

One last thing on choosing your clinic

If you are about to book either treatment, the question to ask the consultation is the same: "Why are you recommending this one?" If the answer is a clear clinical reason connected to what you said you wanted, you are in good hands. If the answer is some version of "this is what we offer" or "this is on promotion this month," you are in the wrong consultation.

I would rather a patient go elsewhere with the right treatment than book with us for the wrong one. We have a five-star review average across 28 patients on Google and we kept it there by being willing to lose a booking now in order to be the clinic the patient comes back to in two years.

Arman Zaki is a GMC-registered Physician Associate and co-founder of Melatone Skin Clinic in Battersea. He delivers polynucleotides personally and refers filler work to Rhianna Beckford (Paramedic) and Vicki Lefeuve (NHS Clinician). Read more about Arman.